






























































LIBRARY OF CONGRESS. 


Chap..Copyright No.- 

Shelf._ 

.K&Lf - 7 — 

UNITED STATES OF AMERICA. 

















t 


ON 


DIABETES MELLITUS 

AND 


GLYCOSURIA 


BY 

/ 


EMIL KLEEN, Ph.D., M.D. 

*1 



PHILADELPHIA 

P. BLAKISTON’S SON & CO. 

1012 WALNUT STREET 
1900 

] 


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t7 , 





PREFACE. 



Among the thousands annually visiting Carlsbad in search of 
health the diabetics present the greatest clinical interest, and from 
my first years as a practitioner in the Bohemian Spa I sought some 
relief from the monotony and many other unsatisfactory aspects of 
a practice of this kind in a careful study of the glycosuric dystrophy 
with its manifold complications. 

Early in the nineties I conceived the project of publishing a 
book upon this subject, hoping thereby to fill a want in the medical 
literature of the day. Others, however, at about the same time 
undertook the same assiduous task. A few months after my 
reading, early in 1895, a paper on “Digestion, Metabolism, and 
Nutritive Needs in Diabetes ” before the Swedish Association of 
Physicians,* v. Noorden’s highly scientific work on diabetes was 
published, and almost simultaneously with the appearance of my 
own long-delayed book in the Swedish language, Naunyn’s mag¬ 
nificent monograph was welcomed by the profession. 

Still, the more than kind reception that has been accorded this 
book by the physicians of my native country has led me to enter¬ 
tain the hope that the most important part of my clinical, experi¬ 
mental, and literary work of recent years has not been entirely in 
vain. I resolved to give my book publicity in some more widely 
used language than the one most familiar to me, and myself, with 
some few additions and changes, translated my book into English. 
In doing this I derived considerable assistance from a dear Ameri¬ 
can friend. Finally, Dr. Eshner, of Philadelphia, has revised the 
manuscript and added his most valuable aid to change my own 


* See the “ Transactions of the Association” (“ Hygiea ”) for the same year, and 
the chapter on Metabolism in this book. In the latter I have added some references to 
the researches of the last few years. 


V 




VI 


PREFACE. 


somewhat deficient English into good English, for which work I 
hereby render my public thanks. For the substance and scientific 
matter of this book I am myself alone responsible. 

I have treated the vast subject of diabetes and glycosuria with 
as much brevity as is compatible with my purpose of giving as 
full a view of it as the present time allows, never having out of 
sight that my chief aim is to facilitate for the general practitioner 
the acquisition of the knowledge of the glycosuric dystrophy, to 
which I have devoted considerable time and work. 

At the end of the book I give a list of names of the chief 
authors on the subject of diabetes but no list of their works, 
as this alone would fill a small volume, and now that we have the 
“ Index Medicus ” and the “ Catalogue,” seems to me entirely 
superfluous. 

Emil Kleen. 

Carlsbad, September, 1899. 


CONTENTS 


Chapter Page 

I. Definition and History,. 9 

II. Geographic Distribution and Etiology,.15 

III. Glycosurias, .26 

IV. Symptoms and Complications of Mild and Severe Diabetes, 70 

V. Diabetes Infantilis,.157 

VI. Diabetes Mellitus Following Extirpation of the Pancreas, 164 

VII. Metabolism and Nutritive Needs,.169 

VIII. Investigation of a Case of Diabetes, .236 

IX. Treatment,.253 

Table of the Commonest Kinds of Food in Percentages of Pro- 
teid, Fat, and Carbohydrate,.295 

Personal Register,.299 

Index .307 




vn 


















DIABETES MELLITUS 


AND 

GLYCOSURIA. 


CHAPTER I.—DEFINITION AND HISTORY. 

Under the name diabetes mellitus are included different pathologic 
conditions which, however imperfectly understood, undoubtedly in 
most cases affect the central nervous system, and which are charac¬ 
terized by a faulty metabolism, as a result of which, under ordinary 
diet, there takes place the excretion in the urine of an abnormally 
large amount of sugar. 

Thus, diabetes mellitus, so far as is at present known, is not a 
clinical unit, but a syndrome, the chief and most constant symptom 
of which is glycosuria, and which is represented by very varying 
clinical types. 

There are, however, numerous cases attended with the excretion 
in the urine of minute yet distinctly pathologic amounts of sugar, 
which cases differ widely in clinical aspect and in prognosis from 
the diabetic type, and which generally are not included in the 
designation diabetes mellitus. 

When the power of consuming the ingested and digested carbo¬ 
hydrates is but little or momentarily impaired, and when the patho¬ 
logic excretion of sugar, under ordinary mixed diet, only slightly 
exceeds the traces of sugar found in normal urine, or is but transi¬ 
tory, the condition is not called diabetes mellitus, but simple 
glycosuria. 

When the excretion of sugar becomes considerable and more 
persistent, but disappears when the carbohydrates are decreased or 

9 


i 


2 



10 DIABETES MELLITUS AND GLYCOSURIA. 

withdrawn from the food, the condition, which generally is accom¬ 
panied by other more or less well-defined symptoms, constitutes 
the mild stage of diabetes. 

The severe stage of diabetes is characterized by the occurrence 
of glycosuria even when the carbohydrates are withdrawn from 
the food. 

We shall find that the limits thus fixed are far more distinct on 
paper than in the reality of clinical experience, in which we see 
represented all imaginable intermediate stages between the normal 
capability of consuming the sugar of the blood and the greatest 
possible deterioration of this capability. 

Our knowledge of diabetes has essentially developed during the nineteenth 
century, but for many ages previously something was known of it, as is shown 
in notices occurring here and there in ancient works. 

The term diabetes (6 : did, through ; fiaiveiv, to go) is attributed to the 
Roman, Celsus, who lived in the beginning of the Christian era. The term 
then probably comprised both diabetes mellitus and diabetes insipidus. 

In the Indian Yajur-Vedas we find definite statements upon this subject, 
and it seems from these ancient documents, discovered about a hundred years 
ago, that Susruta, whose existence was passed in the native land of the 
cobra, the Brahman, and the tiger during the seventh century, was familiar 
with both the clinical picture and the sweet urine of diabetes mellitus, which 
probably then, as now, was more general among the Hindus than among any 
other race. 

Europe was far behind India in knowledge of diabetes mellitus during those 
times. As is always the case, single instances occur of correct guesses long 
before science had acquired the facts. Paracelsus suspected that a change in 
the blood is the cause of the symptoms of diabetes. It was, however, not until 
as late as 1674 that the sweet taste of the urine was first noticed by Thomas 
Willis (1622-1675), and a whole century more elapsed before Dobson showed 
that this sweetness is due to a variety of sugar. The idea of the presence of 
sugar in the blood of diabetics then began to gain ground, and we find this 
opinion general at the commencement of the nineteenth century. Rollo and 
Cruikshank accepted the existence of blood-sugar in diabetes ; but Nicolas and 
Gueudeville, Segalas and Vauquelin, as also Sobeiran, tried in vain definitely 
to demonstrate its presence. Wollaston at first (1811) denied, but afterward 
acknowledged, its existence. Maitland and Ambrosiani (1835) believed they 
had found it. McGregor observed fermentation of diabetic blood, and Simons 
found in the blood of a diabetic patient after a hearty meal 0.25 per cent, of 
sugar, although only traces had been present before the meal. 

All of these observations, however, concerned diabetes exclusively ; but as 
early as 1826 Tiedemann and Gmelin deemed sugar a normal ingredient of 
the blood, and considered that they had proved its presence in dogs, whether 


DEFINITION AND HISTORY. 


I I 

the animals were fed with carbohydrates or with meat. Early in the forties this 
observation was confirmed by Magendie and by Frerichs, and in 1845 Thom¬ 
son, by fermentation, made (far too low) a determination of the sugar in the 
blood of fowls. 

At the close of the forties Claude Bernard began his all-important investi¬ 
gations, which proved successively the presence of sugar in the normal blood 
under all dietetic conditions; its production from glycogen in the liver ; its 
dependence on nervous influences ; its increase above the normal ratio in cases 
of diabetes, and many other facts, a knowledge of which is essential for a 
comprehension of diabetes mellitus* and to which we shall have to return in 
the chapter on Metabolism. 

The enormous amount of work afterward performed in this field by others 
has, on the whole, simply served to prove the correctness of Bernard’s obser¬ 
vations and conclusions, and it is only within quite recent times that experi¬ 
mental pathology has provided us with any material additions to what that 
most admirable physiologist taught us. 

In 1848 Traube observed that sugar disappeared from the urine of a dia¬ 
betic patient when carbohydrates were withdrawn from his food, and that the 
same individual exhibited glycosuria at a later period, in spite of this with¬ 
drawal. He thus discovered the difference between the mild and the severe 
stage of diabetes, on which others, especially Seegen, afterward attempted to 
found a division into two different forms of disease. 

Toward the close of the fifties Briicke and Bence Jones, independently of 
each other, found small traces of sugar in normal urine, an event of import¬ 
ance chiefly because it led to further investigations for small amounts of sugar 
in urine and brought to light many instances of slight glycosuria, pathologic 
though often unessential, that present themselves under different conditions. 
Our knowledge of the simple glycosurias, however, has been chiefly developed 
during the last two decades, and is still increasing year by year. 

Gerhardt, in 1865, discovered that a solution of ferric chlorid causes a wine- 
colored reaction with the urine of patients suffering from severe diabetes. This 
observation has proved of immense importance, as it greatly facilitated the 
diagnosis of severe diabetes and promoted the study and the comprehension 
of certain pathologic metabolic products, and of those acid blood-toxins that 
essentially invest the severe stage of diabetes with its clinical peculiarities. 

Lavoisier had, in the latter part of the eighteenth century, laid down the 
principles of metabolism, but it was not until the middle of the present century 
that our knowledge of this most important subject began rapidly to develop 
through the works of Liebig, G. Lehmann, Bidder and Schmidt, Bischoff, 
Reignault and Reiset, and others. In 1867 Pettenkofer and Voit—though 
they themselves at first misinterpreted their own results—taught us that the 
consumption of oxygen, the excretion of carbonic acid, the production of heat, 
and the nutritive needs in the diabetic are governed by the usual laws, and 
that they are not attended with other deviations from the normal than those 
that arise directly from the loss of sugar through its excretion with the urine. 
When, later, Rubner (in the middle of the eighties) gave us his calorimetric 
tables of the nutritive value of different articles of food, the conditions were 


12 


DIABETES MELLITUS AND GLYCOSURIA. 


fulfilled for arranging a rational diet for diabetics, as for others, and we have 
been enabled more effectually to obviate the mistake of dieting diabetics, with 
the one view in mind of eliminating hyperglycemia and glycosuria, and with 
out due regard to dietetic possibilities and to nutritive needs. 

In 1886 von Mering discovered phloridzin-glycosuria, which is curiously 
characterized by the excretion of large amounts of glucose, with a diminished 
quantity of sugar in the blood. Three years later von Mering and Minkowski, 
thanks to the great accuracy of their mode of investigation, had the good 
fortune to discover that severe diabetes can be produced by total extirpation 
of the pancreas—the one “ artificial ” method at present known of bringing 
about with certainty this variety of diabetes. By reason of these two discov¬ 
eries, and in view of the far-reaching consequences of the latter, von Mering 
must be considered as the investigator that, next to Claude Bernard, has con¬ 
tributed most effectively to our knowledge of diabetes mellitus. 

During the last few decades an extensive literature has accumulated, and 
many valuable contributions have been made to the knowledge of this dystro¬ 
phy. In addition to those already mentioned, a great number of authors have 
distinguished themselves in this connection, among whom I may name Frerichs, 
Bouchardat, Cantani, Seegen, Pavy, Bouchard, G. A. Hoffmann, Griesinger, 
E. Kiitz, von Voit, Naunyn, Ebstein, Chauveau and Kaufmann, Lepine, 
Weintraud and von Noorden—passing over no small number of others who 
have written more or less important works on the subject. 

Diabetes mellitus, being in its “mechanism” a peculiarly mys¬ 
terious disease, with an undiscovered, or at least not fully explained, 
pathologic anatomic basis, has been made the subject of many 
theories, at present amounting to more than thirty. In no other 
department has medicine made such extended excursions into the 
domain of purely speculative science, and nowhere has this led to 
greater liberties with the imagination. ♦ It is not my intention in 
this work, which is designed for the practitioner, to enter upon a 
consideration of all of these thirty theories ; but in order to show 
how weak and uncertain our search for truth has been in this field, 
and how many different theoretic possibilities present themselves, 
I will cursorily mention the main currents of opinions that have 
prevailed. 

In former times the cause of diabetes was looked for in those organs whose 
functions show the most manifest abnormity— i. e ., the kidneys. This idea, 
in all its naivete, has been to a certain degree revived, though with numerous 
modifications, additions, and limitations by our views on phloridzin-glycosuria, 
and by the auxiliary influence on the excretion of glucose, attributed on strong 
grounds by many authors to the kidneys. 


DEFINITION AND HISTORY. 


13 


Rollo, the greatest authority on diabetes at the beginning of the present 
century, supposed the cause of the dystrophy to be a disturbance of the diges¬ 
tive functions, which resulted in an excessive resorption of carbohydrate. 
Similar opinions, however absurd they may seem at present, have been ex¬ 
pressed quite recently by many authors, and, among others, by no less an 
authority than Bouchardat in his earlier days. The importance in the causa¬ 
tion of diabetes of changes in the pancreas was suspected long before Lance- 
reaux wrote his paper on this subject, and before we knew the effect of total 
extirpation of the pancreas, and could assign to this organ a rational position 
in the pathogenesis of diabetes. An intuition of such a relation was at the 
bottom of the views of Bouchardat and others, and later found expression in 
Popper’s idea of faulty digestion, in consequence of a defective secretion of 
the pancreatic juice as a cause of diabetes mellitus. 

Since Bernard’s great discoveries and his theory of the formation of the 
sugar of the blood in the liver from glycogen, and of its consumption in the 
tissues for the production of vital force, two great schools have arisen, in each 
of which several divisions are apparent. One of these schools considers the 
cause of hyperglycemia and glycosuria— i. e ., of diabetes—to be a diminished 
consumption of sugar in the tissues. For the sake of brevity, we may be per¬ 
mitted to say that the other school considers the cause to be an increased pro¬ 
duction of sugar in the liver. According to some views, this excessive produc¬ 
tion, however, is of an entirely passive kind, and is more correctly expressed 
as a diminished capability of the organ of transforming into, and storing as, 
glycogen the sugar conveyed to it through the portal vein, so that a larger 
part of the sugar reaches the circulation by the hepatic veins than can be stored 
in the muscles as glycogen, or be consumed by them. A large number of 
authors consider this view corroborated by the frequency with which sugar 
appears in the urine in cases of cirrhosis of the liver. A positive participation 
on the part of the liver may also be conceived. Claude Bernard and his 
numerous followers believe this to consist in increased activity of a normal 
function pathologically excited by hyperemia. Pavy and Schiff thought the 
production of glucose in the liver an entirely pathologic phenomenon. In 
both views a diastatic ferment and a central nervous influence transmitted 
through the vasomotor nerves are accepted. The latter influence must be given 
a place in every general theory of diabetes. 

Those that have conceived the idea of defective consumption of the sugar 
of the blood have either accepted the disappearance from the organism of a 
ferment that normally should cause decomposition of glucose into glycerin and 
its aldehyd, and the cessation of which embarrasses further oxidation (Schult- 
zen, Schermetjewski, Nencki and Sieber, Bence Jones), or have thought of 
defective oxidation in the lungs (Araki), or have placed the fault with the 
muscles (Zimmer). Since the theory of an “ internal secretion ” of the various 
glands of the body was adopted, and the production of diabetes by total 
extirpation of the pancreas was demonstrated, a large number of scientists 
have come to consider the cause of diabetes to be the disappearance from, or 
the diminution in, the blood of a “glycolytic ferment',” present normally, and 
sent into the blood by the pancreas for the combustion of glucose. 


14 


DIABETES MELLITUS AND GLYCOSURIA. 


There are, moreover, a considerable number of observers who have sup¬ 
posed that there takes place a diminution in, or a retardation of, the entire 
“ internal respiration,” which goes on in all of the tissues,—an opinion which at 
first obtained some support from Pettenkofer and Voit’s experiments on metab¬ 
olism in diabetes by reason of their erroneous interpretation of their results 
(Cantani, Jaccoud, Bouchard, Lecorche, Naunyn, Huppert). 

Diametrically opposed to this opinion is another advocated by Robin, who 
speaks of an increased metabolism, of a “ suractivite de la nutrition." 

In this cursory retrospect I wish to mention also Ebstein’s carbonic-acid 
theory, which, however ingenious, entirely lacks support in facts. Ebstein 
placed reliance on the incorrect but once wide-spread supposition that a 
diabetic ceteris paribus always consumes less oxygen and produces less car¬ 
bonic acid than a healthy individual. The carbonic acid he supposed to act as 
a check on the diastatic (glucose forming) ferment, and also to render certain 
proteids—especially globulins—more tenacious. Thus, when the carbonic acid 
—in consequence of a defect in the protoplasm, with resulting disturbances of 
the “ internal respiration ”—is lessened in diabetes, in the first instance and in 
the milder stage of the dystrophy, the carbohydrate— i. <?., glycogen—is attacked 
by the diastatic ferment more vigorously than under normal conditions. In 
the severe stage the globulins are also decomposed more readily, and an exces¬ 
sive formation of glucose begins at their expense. After Schierbeck’s investi¬ 
gations on the diastatic ferment in alkaline and acid solutions, Ebstein and 
Schultze, in 1893, came to the conclusion that carbonic acid in alkaline solu¬ 
tions augments the diastatic activity, and retards it in neutral solutions, while 
even a very slight degree of acidity inhibits it altogether. It is rather difficult 
to understand how these facts, together with the qualities of the blood under 
normal conditions and in the presence of severe diabetes, could be made to fit 
in with Ebstein’s theory, which, moreover, falls to pieces in the face of the fact, 
now fully proved, that the diabetic produces as much carbonic acid as a 
healthy individual. Ebstein’s citation, in support of his theory, that Hoesslin 
found a sojourn at a high altitude, which had been considered as increasing 
the production of carbonic acid, to be favorable for the diabetic, is an unfortu¬ 
nate one, as Hoesslin’s experience in this respect, at the time his treatise was 
written, was limited to a single case. On such a foundation not even a sup¬ 
position should be hazarded on the subject of diabetes, and far more reliable 
facts indicate that residence at great heights does not in any way counteract 
diabetes. (See the following chapter.) The opinion that a sojourn at a high 
altitude in rarefied air materially increases the production of carbonic acid 
(Mermod, Marcet) does not seem to be borne out by facts. U. Mosso came to 
the conclusion, a few years ago, from investigations conducted on Monte Rosa 
and in rarefied air, that the quantity of carbonic acid produced in respiration 
under these conditions at an altitude of 6400 meters differs but slightly from 
that produced at an altitude of 286 meters (Turin). 

Of late years there have been advanced in France—where, since Ber¬ 
nard’s time, diabetes mellitus has been the object of constant study—theories 
concerning its pathogenesis, in which the nervous system, the pancreas, and 
the liver are all involved. Even if these theories can not as yet be said to be 


GEOGRAPHIC DISTRIBUTION-ETIOLOGY. I 5 

more than hypotheses, they are nevertheless founded on definite observations 
and are of actual interest. I shall, therefore, return to them in the chapter on 
Metabolism, when we shall see that the theories of an increased production 
and of a decreased consumption of sugar both have solid bases, and that they 
ought not to be pitted against each other as utterly irreconcilable. To the 
present comprehension of special pathogenetic factors in the dystrophic group, 
the future will assuredly bring many additions and corrections, and the 
present generation will, perhaps, in time be forced to confess that “ all our 
wisdom was but folly.” 


CHAPTER II.—GEOGRAPHIC DISTRIBUTION—ETIOLOGY. 

Diabetes mellitus is a common phenomenon among civilized 
humanity,* and is constantly increasing in frequency pari passu 
with the intensity of cultivated life. 

Some time ago I saw it stated—I believe it was by Worms— 
that among men occupied in intellectual pursuits (statesmen, learned 
men, professional men, merchants) of an age between forty and sixty 
no less than ten per cent, are diabetics. Most physicians will be 
inclined to protest against this figure as far too high, as it is, if by the 
expression diabetic is meant a person that displays a clinical type 
of diabetes. It would be nearer the truth to place the number of 
diabetics among the classes named at one per cent. On the other 
hand, if we call every person a diabetic that, taking ordinary food, 
excretes habitually and daily an inconsiderable though pathologic 
quantity of sugar in the urine, Worms’ figure would be rather too 
low than too high. If samples of urine be taken an hour after 
dinner from a hundred brain-workers between the ages of forty and 
sixty, it will doubtless be found, on testing with Nylander’s solu¬ 
tion, or with Trommer’s test, verified by the fermentation-test, that 
about fifteen of the hundred samples contain an amount of sugar 


* In animals diabetes mellitus—unless designedly caused for experimental purposes— 
is very rare, but it has been observed in the ape (Leblanc, Beranger-Ferand), the horse 
(Hiibner), and the dog (Thiermesse, Schindelka). Slight glycosuria has also been 
noticed in animals. 




1 6 DIABETES MELLITUS AND GLYCOSURIA. 

that attains to hundredths of a per cent.— i. e., are distinctly patho¬ 
logic. It will, however, also be found that the greater part of the 
“patients ” in question consist of quasi-healthy, or, to use a better 
expression, very slightly affected, persons, who neither for the 
moment present, nor are likely in the future to present, decided 
symptoms of the clinical type that we are accustomed to call 
diabetes. 

Among the European and the American, Aryan, highly civilized 
races, the difference in the frequency of diabetes, on comparing large 
areas, will not be found to be very great: not greater than it may 
be in different parts of the same country. Different conditions of 
life—altitude, climate, and state of culture, even within very narrow 
limits—give rise to very considerable variations. Thus we find 
that diabetes is more common in Malta and Gibraltar than else¬ 
where on the shores of the Mediterranean, in Tuscany than in the 
rest of Italy, in Normandy than in the other provinces of France, 
in Vermont than in the other States of the Union. 


The statistical figures that are available are assuredly far too low, as the 
diabetic type is often not very pronounced, and in the milder form does not 
cause death, except through complications which have no definite relation to 
diabetes. Moreover, these figures have doubtless been obtained in very differ¬ 
ent ways in various places, and allow of no absolute comparison. On learn¬ 
ing from Saundby that the number of deaths annually from diabetes mellitus 
per 100,000 inhabitants is in London 5.88, in Berlin 5.04, in Paris 9.6, in 
Christiania 3.9, in Rome 1.67, in Malta 13.1 (the highest European figure), we 
can scarcely conclude with certainty that the correct figure for Berlin is higher 
than the correct figure for Rome, for which latter city the figure cited is 
assuredly far too low. In Malta, however, diabetes is undoubtedly very 
common. 

In Norway, among 10,000 deaths, 21 are owing to diabetes mellitus (Kiser). 

There is scarcely any doubt that in large communities diabetes mellitus is 
rapidly increasing. According to Bertillon’s statistics (cited from Lepine), dia¬ 
betes caused the following deaths per annum among 100,000 Parisians: 

From 1865 to 1873, a total of 2.3 From 1885 to 1886, a total of II 

“ 1873 “ 1877, “ 4 “ 1887 “ 1892, “ 12.13 

“ 1878 “ 1883, “ 9 

In Copenhagen the mortality from diabetes has also increased rapidly and 
constantly during the past few decades. From i860 to 1864, according to 
Caroe, there was but one death per 62,840 inhabitants, while from 1890 to 1894 
there was one per 12,855. 


GEOGRAPHIC DISTRIBUTION-ETIOLOGY. I 7 

Purdy’s statistics for the United States are demonstrative and show : 

In 1850, 72 per 10,000 deaths. In 1870, 170 per 10,000 deaths. 

“ i860, 98 “ “ <e “ 1890, 191 “ “ “ 

Purdy, undoubtedly with due cause, ascribes the enormous increase after 
i860 to the rapid increase of prosperity, the luxurious mode of life, and the 
more arduous struggle for existence after the Civil War. 

Of all races , the Hindu is most susceptible to diabetes. In India 
and Ceylon diabetes is a very common disease among the upper 
classes,—so common that, according to the editor of the “ Indian 
Medical Gazette,” almost every family in Calcutta belonging to 
these classes of society has lost one or more members by death 
from this dystrophy, while another author (Bose) estimates the 
number of deaths from diabetes in Calcutta at io per cent, of the 
entire mortality (! !!),—a circumstance that must be attributed to 
the highly nervous constitution of the Hindus, their early marriage, 
and excessive sexual life in general, the high intellectual cul¬ 
ture at present prevalent in India among these classes, their 
sedentary mode of life, and perhaps also their diet, so rich in 
sugars and other carbohydrates. The preponderance of male over 
female patients seems to be at least as great as in Europe. Among 
the Mohammedan population in India diabetes, though not rare, is 
not nearly so common as among the Hindus. 

Next to the Hindus the Jews—who in many respects occupy 
the same relative position to Europeans in general as do the Hindus 
to the Jews—are highest in the scale of diabetic frequency. No 
specialist in diabetes can avoid noticing the comparatively large 
percentage of patients among Hebrews, who also are a nervous 
race, and who for centuries have devoted themselves almost exclu¬ 
sively to intellectual and sedentary pursuits. 

It has been of interest to me to form some estimate of the 
frequency of diabetes among the Chinese, who seemed to me, 
during the few weeks I spent among a vast number of their race, 
to be a nation with a highly developed intellectual, but compara¬ 
tively slightly developed emotional, life, rather difficult of compre¬ 
hension for any other than a Chinaman. Saundby’s statements 
seem to prove that diabetes is very rare among Chinese laborers. 
Graham, who at Sumatra practised among 15,000 of them, discov- 


1 8 DIABETES MELLITUS AND GLYCOSURIA. 

ered but a single case during his seven years’ sojourn. In the 
United States, I have myself, from various sources of information, 
come to the conclusion that the disease is far more uncommon 
among the lower classes of the Chinese than among the same 
classes of Americans and Europeans. On the other hand, Dr. 
Cantlie, who for many years has practised in Hong Kong, has kindly 
informed me that among the richer Chinese diabetes is not at all 
uncommon, adding the interesting information that it more espe¬ 
cially attacks those that change from the usual Chinese diet, with 
its preponderance of rice, to a more mixed European diet. I 
presume this observation to be perfectly correct;—just as I have 
repeatedly found that in cases of very slight glycosuria I can cause 
a larger quantity of sugar to appear in the urine by mixed test- 
meals than by those that consist exclusively of carbohydrates. 

Among the contented Japanese, whose education has hitherto 
been Spartan in many respects, diabetes is not common. If, as is 
probable, they ere long provide reliable statistics, it will doubt¬ 
less be seen that with the nation’s wonderful and rapid adop¬ 
tion of European culture, the frequency of diabetes will quickly 
increase. 

Among the Persians diabetes is said to be less general than 
among Europeans, and the same is stated of the Turks (Tholozan). 
Among the Arabs of the part of North Africa under French sway 
the dystrophy is not rare (Calmette and others). 

It is interesting to learn that among the laborers on the sugar- 
plantations of the Mauritius and British Guiana, where, relatively 
speaking, the lower classes consume an enormous amount of cane- 
sugar, diabetes mellitus is rarely encountered (Blair, Saundby). 
From Venezuela the same statement has been forwarded to me. 
Almost all these laborers are “ colored ” and belong to those races 
among which diabetes mellitus is uncommon as a general rule. 
Circumstances, however, seem to indicate that a strongly saccharine 
diet has per se but little etiologic influence. 

Among all people beyond the pale of culture, diabetes is very 
rare. This I believe to be the correct way of viewing the afore¬ 
mentioned immunity among Africans, and the reason why so little 
is heard of diabetes among the Indians of America, or among the 
numerous and various aborigines of Australia, or in the English 


GEOGRAPHIC DISTRIBUTION-ETIOLOGY. I 9 

colonies of mixed but predominant colored population. With 
greater intellectual exertion, keener emotions, higher nervous 
development, more earnest struggle for existence, more urgent 
demands, a more intense culture, in fine, we are bound to find 
more diabetes mellitus. 

From what we have already learned we should a priori be 
inclined to believe diabetes to be far more common among a given 
number of residents in cities than among the same number of per¬ 
sons in the country. There is, therefore, nothing remarkable in 
the large number of statements that support such a supposition. 
On the other hand, it is an interesting fact that statistics point, in 
some degree, in the opposite direction. In Great Britain there are 
several counties with a large urban population which are low in the 
scale of diabetes, while others with a far greater rural population 
are high in the scale. Purdy has compared the figures in the 
United States, and has come to the conclusion that in the North 
diabetes is more general among the rural population, and in the 
South among the urban population ; and he ascribes this difference 
to the better protection against cold afforded by the cities as com¬ 
pared with the country, which holds good only for the North. In 
the South other differences determine the result. These, in my 
opinion, do not, as Purdy supposes, consist in the better oxidation 
secured through the country air, but in the mode of life of the inhabi¬ 
tants of the country, which, as a general rule, is far more free from 
nervous influences. Except during the first decades of life, when 
diabetes mellitus is very rare, and attacks fully as many, or perhaps 
more, girls than boys, this dystrophy is far more common among 
males than among females —naturally, in consequence of the severe 
struggle for existence on the part of men, and their greater prone¬ 
ness to excesses. The difference plainly appears in the second 
decade, and is manifest in all following decades. Generally, there 
are three times as many male patients as female. Exclusive of the 
ages under twenty, Pavy had 928 males and 373 females ; Grube 
had 137 male and 40 female cases, while my own experience shows 
nearly three male to every female patient. 

Diabetes is rare in childhood and youth, the greater number of 
the patients being attacked during the most exacting period of their 
life—from forty to sixty years of age. 


20 


DIABETES MELLITUS AND GLYCOSURIA. 


Pavy’s* table shows : 


Age. 

Male. 

Female. 

Total. 

Male. 

Female. 

Total. 

Under 10, . . 

3 

5 

8 

0.22 

per cent. 

0.36 per cent. 

0.58 per cent. 

From 10 to 20, 

35 

22 

57 

2.57 

it 

0.61 

a 

4.19 

a 

“ 20 to 30, 

69 

28 

97 

5 -o 7 

i i 

2.05 

i i 

713 

a 

“ 30 to 40, 

154 

70 

224 

11.32 

i i 

5-14 

a 

16.47 

(t 

“ 40 to 50, 

260 

79 

339 

19.11 

i i 

5.80 

a 

24.92 

i t 

“ 50 to 60, 

281 

137 

418 

20.66 

i i 

10.07 

i c 

3°-73 

a 

“ 60 to 70, 

138 

44 

182 

10.14 

i i 

3-23 

a 

13-37 

11 

“ 70 to 80, 

25 

9 

34 

1.83 

a 

0.66 

a 

2.49 

(t 

“ 80 to 90, 

1 

• • 

1 

0.07 

i i 

• 

* 

0.07 

i t 


A mild and warm climate seems to give rise to less diabetes than 
a severe and cold one. High altitude tends to increase the fre¬ 
quency of diabetes. The mortality among diabetics is also greater 
during the cold than during the warm season. 

The diabetic patient of Northern Europe passes the winter on the Riviera 
with decided advantage to his health, and his brother in misfortune in North 
America derives benefit from a sojourn in Florida, or in Southern California, 
during the severe cold season. Statistics from the United States speak strongly 
for the unfavorable influence of rigorous climates. According to Purdy, Ver¬ 
mont, with 6.3 deaths from diabetes per 1000 deaths, stands highest in the scale 
among all the States. It is remarkable for its cold winters, and a large part of the 
State is from 3000 to 5000 feet above the level of the sea. Next comes Maine, 
with 4.41 deaths per 1000, and having also a severe climate, though less severe 
than that of Vermont, and at a lower level. As a rule, the “ northeastern hills 
and plateaus ” constitute those parts of the United States that are most favorable 
to the development of diabetes. Purdy gives the mortality from diabetes in 
thirty of the most populous States, the average for all being 1.93 among 1000 
deaths. Taking the figures from Arkansas, Alabama, Texas, Louisiana, 
Georgia, and the Carolinas, I find an average of 0.84 among 1000 deaths, while 
the corresponding figure for Connecticut, Massachusetts, Maine, Vermont, 
Illinois, Wisconsin, Michigan, and Minnesota is 3.21. Although I entirely 
agree with Dr. Purdy that cold and altitude are the chief climatic features that 


* Schmitz, who (1892) had treated 2700 diabetic patients, and who has the largest 
private statistics, furnishes similar figures. I am unable, at this moment, to produce his 
latest table. He practised chiefly at a health resort, and his figures are, therefore, as 
will be easily understood, of less weight than Pavy’s, who obtained his from an estab¬ 
lished urban practice. The English reports of the Registrar-General can not be used, 
as they include both diabetes mellitus and insipidus. 





















GEOGRAPHIC DISTRIBUTION-ETIOLOGY. 


21 


determine high mortality from diabetes, I can not escape the thought that this 
comparison of mine is only apparently so very demonstrative. The figures 
would be conclusive but for the larger colored population and less intensity of 
life and strife in the Southern States. 

Hereditary influences are of great importance in the etiology of 
diabetes. In. a large number of cases it will be found on careful 
investigation* that the diabetic patient is the descendant of a dia¬ 
betic ; and still more frequently, the nervous predisposition, which 
in the patient has found its expression in diabetes, has, in preceding 
generations, shown itself in the form of other affections with well- 
known changes in the central nervous system, in fully developed 
psychoneuroses, or in psychopathic manifestations of various 
kinds. It is often found that several members of the same 
family—brothers and sisters—are diabetic, sometimes exhibiting 
different forms of the dystrophy. Now and again I have found 
slight glycosuria and mild and severe diabetes in members of the 
same family. 

All of the “ learned ” professions provide, comparatively speak¬ 
ing, a vast clinical material for the specialist in diabetes. Physi¬ 
cians especially—who are compelled to devote themselves to study 
assiduously, to sustain great responsibilities, are disturbed at 
night, and are harrassed by the suffering and unreasonable public 
—are often victims of diabetes or exhibit simple glycosuria. 
Statesmen and politicians are still more common subjects of the 
dystrophy in a greater or less degree. The position of the specu¬ 
lator and the business man is best illustrated by the adage from 
Wall Street, New York: “When stocks fall, glycosuria rises.” 
Among the comparatively “ unlearned ” occupations it seems to 


* Close investigation, which in this connection is far more necessary in order to ob¬ 
tain reliable information than under ordinary conditions, is not only troublesome, but is 
attended with numerous difficulties. Many a layman considers neither hypochondria nor 
the slighter forms of melancholia as diseases of the mind, and, as a general rule, he is 
not willing in his own case or in that of his relatives to acknowledge any disorder as 
such that has not been treated in an asylum. Many laymen also entirely disregard 
Graves’ disease, if not very pronounced, slight attacks of epilepsy, etc. Others con¬ 
sciously conceal a history of both psychoses and neurotic tendencies in their own family, 
and feel ill at ease and irritated by being questioned too closely on those subjects. In 
fully a quarter of all cases of diabetes there exists a direct diabetic hereditary predispo¬ 
sition, while a neurotic heredity is present in the great majority. 



22 


DIABETES MELLITUS AND GLYCOSURIA. 


me that sailors furnish the largest contingent of cases of diabetes. 
It is not among the crews, but among the officers, that the greater 
number of diabetic patients will be discovered. I must have seen 
a score of sea-captains, usually affected but slightly, middle-aged, 
often corpulent, whose voices and figures often remind one of 
“ Captain Cuttle.” The great responsibility, the disturbed sleep 
at night, the good table, the drinks, and the limited exercise, possi¬ 
bly also the low temperature prevailing on board, all contribute to 
the development of diabetes. 

The presence of pathologic quantities of sugar in the urine is 
far more common among the higher classes, with their more nervous, 
sedentary, and luxurious mode of life, than in the lower classes. 
On the other hand, a far greater percentage of cases of diabetes 
occurring among the last-mentioned classes is of the severe kind 
than is the case among well-to-do people. In making this state¬ 
ment I am perfectly aware that the less serious variety of diabetes 
is more often overlooked or neglected by the poor than by the rich, 
and that for this reason, also, far fewer mild cases are treated in 
the public hospitals than in private practice. 

At Carlsbad, with a visiting public consisting almost exclusively of persons 
of some means, I not rarely discover a case of previously overlooked mild 
diabetes, and far more often cases of slight glycosuria. For a number of 
years, during the winter, in the capacity of physician in one of the dispensaries 
for the poor in Stockholm, I had ample opportunities of proving how compara¬ 
tively rare glycosuria is among such patients. 

Among occasional causes painful, depressing, or irritating emotions 
must doubtless be placed first. The patient often—and doubtless 
correctly—states the cause of his disease to be constant vexation 
in consequence of changes in external circumstances, grief at the 
loss of wife, husband, child, etc. In far rarer cases a violent fit 
of anger or fright—influences that invariably increase glycosuria in 
a diabetic and at times engender an occasional attack in a healthy 
individual—may give rise to a real, even severe, form of diabetes. 
One of my Carlsbad patients,—long ago deceased,—a brave and 
loyal officer of the Prussian Guards, dated both his Iron Cross and 
his diabetes from that fearful time outside St. Privat, before the 
longed-for order to storm was given. (See Glycosurias.) 

Intellectual overexertion , and more especially the tiresome, unin- 




GEOGRAPHIC DISTRIBUTION-ETIOLOGY. 23 

teresting acquisition of sterile facts, also plays a certain role in the 
etiology of diabetes. In Sweden, where an enormous amount of 
time is spent at the universities in preparing for examinations, 
more than one case of diabetes in early years has come under my 
observation, in which the “corpus delicti” was probably the 
“ cramming.” 

Sexual excesses , both natural and unnatural, doubtless are most 
deleterious. Here, as always, we find that what in one person 
causes diabetes, in another causes glycosuria, and the presence of 
small quantities of sugar in the urine in cases of sexual neuras¬ 
thenia—especially in youths that have practised much masturba¬ 
tion—is not uncommon. Such an occurrence is sometimes only 
transient; but at other times diabetes develops in persons of middle 
age, in whose case no other point of importance can be discovered 
in the history than neurasthenia acquired in youth in the manner 
described. The sudden enormous increase in the frequency of 
diabetes just about the fifteenth year of life and the first manifesta¬ 
tion of its preponderance among males as compared with females 
at this time, is doubtless owing partly to the strained intellectual 
activity often entered upon even at that early period, but also in 
part to masturbation, which is then so often practised. Both of 
these causes are far more prevalent among boys than among 
girls. 

Some of our habitual luxuries that powerfully affect the nervous 
system certainly exercise a predisposing influence in the development 
of diabetes. This is principally the case with spirits for the occa¬ 
sional effects of which I must refer the reader to Alcoholic 
Glycosuria. I suspect, however, that a similar influence is exerted 
by other habitual poisons, and my attention has been called especially 
to the frequency of glycosuria in patients suffering from what we 
(incorrectly) term “ nicotin poisoning,” as a result of excessive 
smoking. This statement is made with a full realization of the 
difficulty, if not impossibility, of furnishing anything approaching 
statistical proof of its accuracy. 

A sedentary life seems to favor the development of diabetes mel- 
litus, which is seldom found in laborers, and is deemed by many to 
arise from decreased consumption of the blood-sugar in the 
muscles. 


/ 


24 


DIABETES MELLITUS AND GLYCOSURIA. 


Profuse consumption of carbohydrates, especially of sugar, is often 
mentioned among the etiologic factors of diabetes. It stands to 
reason that any article of food that always increases glycosuria in 
diabetics will, if taken in large quantities, predispose to this dys¬ 
trophy ; nor can it be denied that a large number of diabetics have 
been fond of sweets. For my part, however, I am inclined to 
think that, on the whole, it is too rich a diet, both as regards the 
mixed nutriment, and more especially as regards alcohol, that plays 
the predominating role in this connection, and that the importance 
of large quantities of starch and sugar has been exaggerated. I 
beg to remind the reader that no carbohydrate other than grape- 
sugar causes glycosuria* in healthy individuals, and that laborers 
on sugar plantations show no special disposition to glycosuria or 
diabetes ; and, finally, that just those classes in China and Japan 
that live almost exclusively on rice enjoy almost complete immu¬ 
nity from diabetes. 

Starvation, especially if continued for any length of time, doubt¬ 
less predisposes to diabetes. I refer the reader to the glycosuria 
following starvation, discovered by Claude Bernard, and mqre 
closely investigated by Hofmeister. (See the following chapter.) 
This form of glycosuria, however, is generally of short duration, 
although cases are sometimes encountered in practice in which 
insufficiency of food seems to be the immediate cause of severe 
diabetes. 

Some time ago I attended a girl, eleven years of age, in whose case a care¬ 
ful investigation failed to reveal any other etiologic factor than insufficiency of 
food. For two months the child had been visiting some very poor relatives, 
and during that time had been constantly underfed. On her return, when she 
resumed her usual diet, severe diabetes set in. (See case, chapter v.) 

Exposure to cold, if severe or often repeated, is universally con¬ 
sidered one of the causes of diabetes. 

Trauma now and then may undoubtedly cause diabetes, which 
sometimes follows immediately, but sometimes not until months 
have elapsed after the accident. The development of diabetes 
under these circumstances is more likely to follow trauma of the 


* The glycosurias of the Trappists who make their liqueur (Charcot); of the German 
students who consume large quantities of ale (Kratschmer); or of Swedish students who 
drink arrack and sugar or Swedish punch, are examples of alcoholic glycosurias. 




GEOGRAPHIC DISTRIBUTION-ETIOLOGY. 2 5 

head; Griesinger was the first to call attention to -the fact that 
contusions of various parts of the body, however distant from the 
nervous centers, may lead to a similar result. Nevertheless, only 
an exceedingly small percentage of traumata give rise to diabetes, 
and such accidents, though common, do not act as a cause in more 
than about one per cent, of all cases of diabetes in adults. Among 
nearly 200 of my own cases of diabetes in which the etiology has 
been carefully investigated, I find only two cases in which I con¬ 
sider trauma the cause with practical certainty. Among diabetic 
children, however, the percentage is larger. 

Finally, sunstroke is, in rare cases, mentioned as a plausible cause 
of glycosuria or diabetes. 

There are two dystrophies that have some, though as yet un¬ 
explained, connection with diabetes mellitus, and which undoubtedly 
constitute a predisposition to it—viz., obesity and gout. 

All three of these dystrophies are not rarely present in the same 
family, and sometimes even in the same individual. 

For other pathogenetic points I must refer to the next chapter. 
All the evidence seems to indicate that whatever may, as a tran¬ 
sient or less profound influence, cause glycosuria, may, as a more 
persistent or more profound influence, cause diabetes in a mild or 
in a severe degree. 

Diabetes, like all other dystrophies, is sometimes found in hus¬ 
band and wife, and Schmitz conceived the original, but not well- 
founded, idea that this may be the result of direct diabetic infection. 
I have myself seen several such instances in practice, just as I have 
seen married couples suffer from gout and adiposity, and I have 
always favored other explanations, too evident to any one to detain 
us further, which seem more rational than the theory of a diabetic 
infection. Tessier, however, has written a thesis in which this asso¬ 
ciation receives further consideration. 


3 


26 


DIABETES MELLITUS AND GLYCOSURIA. 


CHAPTER III.—GLYCOSURIAS. 

Since Briicke and Bence Jones found a reducing and fermenting 
substance in normal urine, the presence of minute quantities of sugar 
in the urine of healthy persons, and its possible amount within physi¬ 
ologic limits, have been much discussed. As representatives of 
the extreme views on this subject I may mention, on the one hand, 
Seegen, who, particularly in the beginning of his career, attributed 
vast pathologic significance to the slightest trace of sugar in the 
urine ; and, on the other hand, we have Kuhne, who considered 
o.i per cent., and Roos, who even mentioned 0.3 per cent., as 
possible under normal conditions. Breul has recently estimated 
the amount of sugar in normal urine as varying between 0.04 and 
0.2 per cent. The larger amount is reached especially, he thinks, 
with a small expenditure of heat, high surrounding temperature, 
and bodily rest. 

From the researches of Abeles, Wedenski, Schilders, Moritz, and 
Baisch, and a large number of my own investigations, I have come 
to the conclusion that there is a trace of glucose in normal urine, 
and that the amount in twenty-four hours scarcely exceeds a 
thousandth of 1 per cent. Some slight or occasional increase 
beyond this may often occur without noteworthy significance, but 
as soon as we reach hundredths or tenths of a per cent, we are within 
pathologic limits. The finding by Worm-Muller of sugar in 18 and 
by Nylander in 14 samples of urine from 100 “ healthy ” individuals 
by their tests, of which neither yields a reaction in the presence of 
less than a hundredth of a per cent. ; and a similar experience on 
the part of Breul with Fischer’s test, are for me evidences of the 
great commonness of slight but pathologic glycosuria, and I have 
always observed that such individuals, though they can not be pro¬ 
nounced diabetics, are not perfectly healthy, but will be found to 
suffer from nervous or gouty or other disorders. 

As experimental pathology has of late proved that various 
operations, especially on the nervous system, cause excretion of 
sugar, so also has clinical experience shown that glucose may 
occur, over and above the normal traces, under several pathologic, 
but otherwise entirely dissimilar, conditions, some of which are of 


GLYCOSURIAS. 


2; 


a passing nature, though others may last for the greater part of 
a-long life. We should never disregard or pass over without 
thorough investigation a measurable quantity of glucose in the 
urine ; but we must avoid attaching too great an importance to the 
excretion of minute amounts, even if repeated daily, and pro¬ 
nouncing at once as diabetic every person whose urine yields a 
positive reaction to tests for grape-sugar. It is now impossible to 
change the clinical and prognostic idea that physicians and laymen 
alike for centuries have attached to the expression diabetes melli- 
tus. A person that, upon an abundant mixed food, excretes, e.g., 
0.5 gram of glucose in the twenty-four hours is no diabetic in this 
sense, even if this insignificant excretion is maintained for years. 
Such manifestations occur more especially, and in large numbers, 
among neurasthenic and among gouty patients. The division of 
all the various forms and conditions attended with pathologic excre¬ 
tion of glucose into simple glycosuria, mild and severe diabetes is 
the one that best corresponds to the clinical reality, and the only 
one that seems to me possible at the present day. 

A rational classification of the different forms of simple glyco¬ 
suria is at present entirely impossible, owing to our defective knowl¬ 
edge of pathogenetic details ; we must, for the time being, content 
ourselves with a table. At the head of the list we place alimentary 
glycosuria, common alike to healthy and to diabetic persons after 
the ingestion of large quantities of grape-sugar. Next come the 
glycosurias that arise from disorders in those organs that, even 
though the modus operandi is not as yet completely understood, 
undoubtedly influence directly the metabolism of the carbohy¬ 
drates : the nervous system, the pancreas, and the liver. The 
nervous glycosurias may be subdivided into organic and functional , 
with known or unknown lesions of the nervous system. (The 
former include a number of experimental glycosurias.) Lesions in 
the pancreas may give rise to simple glycosurias, or to mild or 
severe diabetes ; but the pancreatic glycosurias are treated of at 
length in a special chapter, and are therefore omitted from further 
consideration here. There are also hepatic glycosurias , but these 
are only known imperfectly from experimental and clinical obser¬ 
vations. 

Among toxic glycosurias , that due to alcohol possesses the 


28 


DIABETES MELLITUS AND GLYCOSURIA. 


greatest practical importance ; and those due to phlondzm and to 
carbon monoxid , the greatest theoretic interest. Among glycosurias 
from infection , those that complicate malaria or influenza are the 
most common. In this category we include also that excretion of 
sugar in the urine that has been observed in association with puru¬ 
lent processes. Among “ concomitant ” glycosurias, special stress 
should be laid on those that occur in conjunction with obesity , gout , 
and diabetes insipidus , all of which are allied to diabetes mellitus. 
Glycosuria sometimes arises, further, from cold , from starvation , and 
from fatigue . It may occur, also, in the fetus y and it may be of 
puerperal origin. Finally, pathologic quantities of sugar are often 
observed in the urine in senility and in cachectic states. Of late 
years much has been written of renal glycosuria, and there seems 
to be no doubt that the kidneys have some influence on the excre¬ 
tion of sugar. The glycosuria from phloridzin may also be 
included in the renal variety. With regard to the glycosuria that 
is attributed to cardiac disease (Reynoso, Neumann), our knowledge 
seems at present to be too scanty to permit of any conclusion. 

Of all these forms of glycosuria the acute alcoholic and the 
chronic functional neurotic, and the equally chronic gouty, are 
the most common, occurring much oftener than all the others 
together. 

One attribute is common to all nondiabetic glycosurias with the 
exception of the one caused by phloridzin : viz., the excretion of 
sugar in varying, though never considerable, amount. The gly¬ 
cosurias are, so far as measurable quantities are concerned, transi¬ 
tory in some sense. Thus, after the ingestion of a large amount 
of glucose, after intoxication, cold, starvation,, fatigue, or violent 
emotion, the sugar appears in the urine only for a short while,— 
sometimes only for hours,—and then generally disappears, never to 
return. After infections, childbirth, etc., sugar may appear in the 
urine for a number of days, but rarely persists for more than a 
few weeks. In cases of neurasthenia, gout, and obesity, or in 
senility and other more permanent states, the glycosuria may reach 
measurable amounts for only a short while some time after meals, 
and it may remain stationary at this point for years ; though every 
now and then, as sometimes happens also after transitory influences, 
it may be converted into true diabetes. 


GLYCOSURIAS. 


2 9 


Glycosuria is in most cases an immediate effect of hypergly¬ 
cemia, or the presence of an increased amount of sugar in the 
blood, though the relation between the blood-sugar and the urine- 
sugar is not a perfectly fixed one, and some influence on the part 
of the kidneys must be accepted. (See below.) Claude Bernard 
found that the dog, whose blood contains normally about from 
o. io to 0.15 per cent, of sugar, begins to exhibit glycosuria when 
the hyperglycemia reaches from 0.25 to 0.30 percent. I accept 
the normal glycemia in man as varying between o. 10 and 0.15 per 
cent., and from the figures of Seegen and others it must be con¬ 
cluded that glycosuria may appear when the amount of sugar in 
the blood is only slightly above the last-named figures (even below 
0.20 per cent.). 

Hyperglycemia is, however, not a necessary prerequisite for gly¬ 
cosuria. The quantity of sugar in the blood is abnormally low in 
phloridzin-glycosuria. The same condition exists, according to 
Dastre, in the glycosuria due to slow asphyxiation. Hibernating 
animals, according to some observations, exhibit glycosuria; 
although the quantity of sugar in the blood diminishes during 
hibernation, and increases rapidly as the animals resume their 
accustomed activity (Claude Bernard), and their glycosuria disap¬ 
pears. According to Bernard, the amniotic fluid of the fetus (its 
urine) often contains sugar. The normal glycemia of the fetus is, 
so far as I know, not yet satisfactorily determined, but it seems to 
me possible that we might have here another example of hypo¬ 
glycemia with glycosuria.* 

Alimentary glycosiiria occurs normally after the ingestion of 
large quantities of glucose, and it is of great importance to remem¬ 
ber that, so far as human beings are concerned, this is the sole 
physiologic variety of purely “alimentary” glycosuria—which ex¬ 
pression is often incorrectly applied. The largest possible quan¬ 
tities of ingested starch cause no glycosuria in healthy persons. 
After the ingestion of large quantities of sugars other than glucose 

* On the other hand, Naunyn mentions cases in which the amniotic fluid of the fetus 
contained no sugar, even when the mother suffered from diabetes; this fluid, in other 
cases of diabetes, may contain quite a considerable quantity of glucose (0.7 per cent., 
Husband). 



30 


DIABETES MELLITUS AND GLYCOSURIA. 


the urine will be found to contain normally only a small part of 
the same kind of sugar ; we thus may have a physiologic saccha- 
rosuria, a lactosuria, laevulosuria, etc. (see below). 

Alimentary glycosuria evidently is caused by failure on the part 
of the liver to transform into glycogen very large quantities of glu¬ 
cose entering into that organ through the portal vein. The excess 
that is not transformed or is not stored or consumed in other 
organs (muscles) passes into the urine. 

Numerous experiments of my own with glucose in normal and 
diabetic individuals have confirmed essentially several facts pre¬ 
viously observed by Worm-Muller, Kiilz, and others, and have 
taught me : (i) That normal individuals can take, some hours after 
a light breakfast, and before the second meal of the day, generally 
ioo, often 200, grams of glucose without excreting a measurable 
amount in the urine. The maximum average amount that can be 
taken under such circumstances is probably below I 50 grams of 
glucose. (2) That this maximum amount—or, in other words, the 
limit of assimilation (Hofmeister)—varies vastly, even in normal in¬ 
dividuals, under different, and sometimes even under apparently 
similar, conditions. (3) That the capacity for taking glucose with¬ 
out the development of glycosuria is often greater earlier than later 
in the day. (4) That a healthy individual excretes, as a rule, far 
less after the same amount of glucose than does a diabetic ; but (5) 
that a diabetic in the mild stage of the disease may, by prolonged 
abstinence from carbohydrates for the time being, attain an equally 
high power of assimilation as a normal individual; and (6) that, 
consequently, a simple ingestion of glucose can not, for more than 
the time being, determine the limit of assimilation, and can not 
always establish the absence or presence of diabetes. 

Under organic nervous glycosmna are included those cases of 
slight excretion of sugar in the urine that occur in conjunction with 
known lesions of the cerebrospinal and sympathetic nervous system. 
Experimental pathology has evolved some valuable contributions 
to our knowledge of central action in this connection ; but this 
knowledge, however, is very imperfect.* Clinical experience 

*The technical difficulties in the way of full and exhaustive investigation are scarcely 
to be overcome. Kahler’s experiments, which, unfortunately, only concerned polyuria, 




GLYCOSURIAS. 


31 


throws but a faint light on the subject, which is somewhat increased 
by pathologic anatomy. (See below.) 

Though isolated observations as to the connection between cer¬ 
tain lesions of the nervous system and glycosuria (or diabetes) had 
previously been made, it was Claude Bernard who, in 1849, first 
demonstrated this relation by his celebrated “ piqure ” in the floor 
of the fourth ventricle between the centers of the pneumogastric and 
acoustic nerves. This lesion causes a transitory hyperglycemia, 
coupled with polyuria, and the presence in the urine of glucose to 
the amount of several parts to the hundred for from five to six hours 
in the rabbit and about forty-eight hours in the dog.* Puncture a 
little higher, in a frontal direction, causes albuminuria, while another 
somewhat lower causes simple polyuria. Bernard and many others 
have considered these phenomena symptoms of irritation, not of 
paralysis. As irritation of the chorda tympani causes increased 
functional activity (and hyperemia) of the submaxillary gland 
through the influence of sympathetic fibers, which preside over the 
vessels and lead to their distention, so is a vasomotor center in the 
brain irritated by Bernard’s puncture. The stimulation is then 
transmitted through the upper part of the spine, and afterward 
through the splanchnic nerves to the vessels of the abdominal 
organs in which hyperemia plainly manifests itself. By the in¬ 
creased flow of blood to the liver its glycogen is attacked more act¬ 
ively than usual by the diastatic ferment in the blood, and the pro¬ 
duction of sugar is increased, according to Claude Bernard. The 
great physiologist undertook the experiment for the purpose of irri¬ 
tating the center of the pneumogastric nerve, and expected glyco¬ 
suria from this excitation. He discovered, however, that glycosuria 
appeared after the puncture even if both pneumogastric nerves were 


seem to have given technically the best results. He injected a concentrated solution of silver 
nitrate through a fine cannula, and thereby caused circumscribed destruction in different 
parts of the brain of the rabbit. Lesions of Eckhard’s “ lobus hydruricuset diabeticus ” 
caused transitory and inconstant polyuria, which also resulted from a lesion of Deiter’s 
nucleus and adjacent parts of the crura cerebelli. A lesion of the acoustic tubercle 
and acoustic striae caused polyuria within forty-eight hours. Although these results 
hold good for rabbits, they can not be applied without further experiment to other 
animals. Kahler favored the theory of stimulation. 

* Bernard’s puncture also caused glycosuria in pigeons (Bernard) and in frogs (Schifif, 
Kiihne). 



32 


DIABETES MELLITUS AND GLYCOSURIA. 


cut; that no glycosuria followed irritation of the peripheral stump ; 
that glycosuria may be caused by reflex action, if the central stump 
is irritated, but that no glycosuria follows the puncture if previously 
both splanchnic nerves are cut or if the pancreas and the liver are 
separated from the nervous system. The puncture is now known 
to have the usual effect even if the pancreas is extirpated, and then 
increases the hyperglycemia (Kaufmann) and the glycosuria 
(Hedon), but it does not have that effect if the celiac plexus is 
extirpated (Schiff). After the glycosuria is over, the glycogen of 
the liver has mostly disappeared. If this has been previously re¬ 
moved by starvation, no glycosuria follows the puncture. If a 
certain quantity of glucose is injected into the mesenteric veins of 
an animal that has lost its glycogen through starvation, a slight 
glycosuria follows. A much more pronounced glycosuria follows, 
under otherwise the same circumstances, if the injection is preceded 
by Bernard’s puncture (Naunyn), and it is thus evident that the 
capacity of the liver for storing glucose as glycogen is diminished 
by the puncture. Though the glycosuria following Bernard’s 
puncture is transitory, and not very considerable, postmortem 
observations (see below) indicate that permanent changes in the 
floor of the fourth ventricle cause real diabetes, and Bernard’s punc¬ 
ture has been a factor of great importance in our comprehension of 
diabetes mellitus. 

Eckhard found that stimulation of a part of the vermis (“lobus 
hydruricus et diabeticus ”) is followed by polyuria and glycosuria. 

Lesions of various parts of the brain may cause glycosuria, as 
Schiff saw after section of the optic lobes, the pedunculi cerebri, 
and the central and posterior parts of the pedunculi cerebelli. 

Glycosuria often occurs after trauma of the brain. Higgins and 
Ogden found it in 20 out of 212 cases. This glycosuria generally 
passes off in a few days ; now and then true diabetes mellitus or 
insipidus remains. Though Asher has collected 124 cases of trau¬ 
matic diabetes mellitus, I repeat that trauma is a rare cause of 
diabetes mellitus in adults. 

Section of the spinal cord down to the fourth cervical vertebra 
is followed in the dog by glycosuria (Pavy, Chauveau, and Kauf¬ 
mann). 

Section of the spinal cord between the fourth cervical and the 


GLYCOSURIAS. 


33 


sixth thoracic vertebra is at first followed by slight and transitory 
hyperglycemia, but subsequently by hypoglycemia. Incisions 
below the sixth thoracic vertebra cause no alteration in the quan¬ 
tity of the sugar in the blood (Chauveau and Kaufmann). 

Claude Bernard severed the spinal cord of a rabbit between the last cervical 
and the first dorsal vertebra. The animal became paralyzed below the divi¬ 
sion, and respiration became slower, and the temperature sank. The quantity 
of sugar in the blood also diminished,—as Chauveau and Kaufmann found 
also subsequently,—and the amount of glycogen in the liver increased. This 
last fact is denied by Chauveau and Kaufmann, who aver that though the 
liver, after this operation, certainly gives off less glucose to the blood, it instead 
discharges more glycogen (?). 

If the pneumogastric of one side is cut and the central stump is 
irritated, glycosuria follows, and persists for a few hours. Some¬ 
times it arises merely in consequence of the section (Bernard, 
Eckhard, Kiilz). Arthaud and Butte caused a more continuous 
glycosuria (amounting almost to 2 per cent.) by maintaining an 
inflammatory process in the central stump. Couvreur, after sever¬ 
ing both pneumogastric nerves, saw glycosuria develop in the 
rabbit, and found, after the same experiment in the pigeon, that the 
amount of sugar in the blood first rises above, but afterward falls 
below, the normal. 

Filehne saw glycosuria appear on irritation of the depressor branch of the 
pneumogastric nerve, perhaps from the passage of the stimulus to the latter. 

Claude Bernard and others have found that irritation of the 
peripheral stump of the divided pneumogastric nerve does not 
cause any change in the amount of sugar in the blood under the 
same conditions. Arthaud and Butte and Lepine observed hyper¬ 
glycemia, and Morat hypoglycemia. These differences in results 
may possibly be explained by differences in division of the nerve- 
fibers in the trunks of the pneumogastric. 

Niedieck caused inflammation of the sciatic nerve in the rabbit, 
and found glycosuria develop. The neuritis had spread to the 
spinal cord, and at times it had passed over to the sciatic nerve of 
the other side. Niedieck considers that changes in the spinal cord 
cause the glycosuria, either by directly modifying the abdominal 
circulation or by transmitting the irritation to the floor of the fourth 
ventricle. 


34 


DIABETES MELLITUS AND GLYCOSURIA. 


Schiff also found that irritation of the sciatic nerve caused glyco¬ 
suria, which might last for several days and reach two per cent. 
This was afterward observed also by Ryndsjun, Bohm and Hoff¬ 
mann, and others. The expeiiment does not always succeed in 
inducing glycosuria, although Kulz obtained it in nine of ten 
cases. 

Butte saw glycosuria after irritation of the first pair of dorsal 
nerves. Frerichs, Frazer, and others have observed glycosuria in 
the course of rheumatic inflammation of different nerves, and it is 
probable that irritation of any nerve, if sufficiently intense, may 
bring about such a result. 

A number of observations illustrate the influence of the sympa¬ 
thetic nervous system on the sugar in the blood. 

As early as 1859 Pavy found sugar in the urine after section of 
the nerves that proceed from the superior cervical ganglion, or after 
extirpation of the ganglion. 

Cyon and Aladoff observed glycosuria after section of the inferior 
cervical ganglion, of the superior thoracic ganglion, and of annulus 
Vieusseni. 

Kulz found section of the cervical sympathetic trunk to cause 
slight glycosuria in four of ten cases ; while irritation of the cen¬ 
tral stump several hours later was followed by glycosuria in six of 
the ten cases. 

Irritation of the thoracic division of the sympathetic nerve also 
causes glycosuria (Pavy). 

Morat and Duponc observed an increased production of sugar in 
the liver as a result of irritation of the splanchnic nerve. 

Section of the splanchnic nerves often causes glycosuria. Hans 
Voit, however, failed recently to obtain this result in the majority 
of cases. 

Pincus, Budge, and Lamanski saw dogs, rabbits, and cats die with 
profuse diarrhea and a violent gastro-enteritis about twenty-four 
hours after extirpation of the celiac plexus. By means of the same 
operation Munck and Klebs induced atrophy of the pancreas and 
glycosuria; while Lustig observed neither diarrhea nor atrophy 
of the pancreas, but considerable glycosuria (with polyuria), ace- 
tonuria, albuminuria, and death in coma. Peiper had a similar ex¬ 
perience with rabbits, the glycosuria reaching from 2.5 to 4 per 


GLYCOSURIAS. 


35 


cent., but neither it nor the acetonuria nor the albuminuria was 
constant. 

A. and E. Cavazzani found a great increase in the quantity of sugar 
in the blood in the hepatic veins after mechanic and electric stimu¬ 
lation of the celiac plexus. 

A. Cavazzani and G. Soldani, who consider the production of 
sugar in the liver to be a secretion, like all other secretions, found 
that atropin, which paralyzes the sympathetic centers and diminishes 
secretion, also diminishes the amount of sugar in the hepatic veins, 
probably by paralyzing the celiac plexus. 

Clinical experience affords numerous illustrations of the depend¬ 
ence of the assimilation of carbohydrates on the nervous system. 
Sugar has been found in the urine in cases of general progressive 
paralysis (Lallier, Bequerel, Bond, Strauss), of tabes dorsalis (Smith, 
Oppenheim, Eulenburg, and others), of multiple sclerosis (Weich- 
selbaum, Mile. Blaine Edwards, Richardiere), of paralysis agitans 
(Huchard, Topinard, Naunyn), of chorea minor (Demme, and 
others), of epidemic cerebrospinal meningitis (Mannkopf), and of 
cerebral meningitis (Naunyn), of syphilis (Leudet, Frerichs, and 
others), of aneurysm and of new growths (v. Recklingshausen, 
Frerichs, Seegen, Richardson, Spitzka, De Jonge, and others), of 
cerebral softening (Naunyn, and many others) and cerebral hemor¬ 
rhage (Frerichs, Olivier, Schiitz, Jacques Meyer, and others). 
Michael also found a cysticercus embedded in granulations in the 
floor of the fourth ventricle in a case of diabetes. 

The numerous cases of disease of the brain, attended with the 
presence of pathologic quantities of sugar in the urine, permit us 
to conclude with certainty that a causal connection exists between 
lesions of different parts of the brain and glycosuria; but the 
statistics on the subject are of little value, on account of the great 
frequency of glycosuria independently of brain disease, the small 
number of cases, and the want of uniformity in investigation and of 
exact expression for the normal power of assimilation. It must be 
acknowledged that in a large number of cases of brain disease there 
is only an insignificant decrease, if any, in the power of assimilating 
carbohydrates. In only four of Kahler’s twenty-three cases of 
organic disease of the central nervous system was there a distinct 
diminution in that power. Van Oordt (1898) found enfeebled power 


36 DIABETES MELLITUS AND GLYCOSURIA. 

of assimilating carbohydrates in 25 of 178 cases of diseases of the 
central nervous system. Several of the cases were neuroses (neu¬ 
rasthenia, hysteria, traumatic neurosis). Epilepsy and diseases of 
the spinal cord seemed to cause a diminution in the power of assimi¬ 
lation. Van Oordt’s twenty-five cases, however, do not seem to me 
to make up a greater percentage with decreased power of assimilation 
than is found, on the average, among brain-workers. Glycosuria 
seems to be most frequent in cases of tumor of the brain, of 
general progressive paralysis, and of cerebral hemorrhage. The 
intensity of the glycosuria is generally slight, and does not amount 
to a real diabetes. Still, in cases of general paralysis, the amount 
of sugar often reaches one per cent, or more, and in cases of 
tumor and hemorrhage as much as four per cent, has been ob¬ 
served. If the patient survive, the glycosuria following apoplexy 
generally is transitory; sometimes true diabetes may develop 
(Jacques Meyer). (For a consideration of glycosuria complicating 
tabes dorsalis and multiple sclerosis I refer to chapter II.) 

Cerebral softening, or encephalomalacia, is much more commonly 
an effect than a cause of diabetes (Naunyn). 

Exophthalmic goiter is sometimes attended with glycosuria 
(Chvostek, Dumontpellier, Panas, Pavy, Blocq, Kraus, Ludwig, and 
others), and sometimes with true diabetes (Bettman, Laache). I 
have at present under observation a case of diabetes with struma, 
tachycardia, and nervous symptoms, but without exophthalmos.. 

A diminished power of assimilation of carbohydrates in different 
degrees has often been observed in cases of akromegaly also 
(Pierre-Marie, Cunningham, Lancereaux, and others). Marinesco 
has recorded a case of akromegaly with diabetes mellitus, epilepsy, 
and bilateral hemianopsia. 

Epilepsy is at times, especially after attacks, attended with gly¬ 
cosuria (Goolden, Griesinger, Lallier, Ringer, Barlow, and others). 
“ Mais elle (la glycosurie) reste en somme une manifestation excep- 
tionelle ” (“ Les Epilepsies, ” Ch. Fere, Paris, 1890). 

Pathologic quantities of sugar have also been discovered in the 
urine in cases of meningomyelitis (Kunkler), of myelitis (Bequerel), 
of spinal hemorrhage (Siebert, Scharlau, Vogler), of fracture and 
contusion of the cervical and dorsal vertebrae (Schiff, Frerichs, 


GLYCOSURIAS. 


37 


Fischer), and of spondylitis (Baum). May found glycosuria and 
levulosuria in a case of transverse myelitis. 

Traumatic neuroses are often accompanied by glycosuria (Brou- 
ardel, Richardiere, Strauss, von Striimpell, Ebstein, Naunyn, and 
others). 

Simple neuralgias also—especially of the fifth pair—and sciatica 
are often complicated by glycosuria. I recently found one per 
cent, of sugar in the urine in a case of violent sciatica without any 
other symptoms of diabetes. 

I consider it one of my most important tasks to emphasize the 
glycosuria so often found in cases of acute or chronic “functional ” 
nervous disturbances, and for which there is no better name than 
functional nervous glycosuria. 

Such a pathologic excretion of sugar may be the effect of an 
entirely transitory nervous disturbance, and may appear in other¬ 
wise healthy individuals for only a few hours after some powerful 
emotion (as of fear or anger), such as in a case of more permanent 
glycosuria, or in one of true diabetes, may for a short while greatly 
increase the quantity of sugar in the urine. Almost every physi¬ 
cian who has given much attention to a study of the urine will have 
encountered instances of such transitory glycosuria, of which a 
large number are recorded in literature. Many facts tend to show 
that a similar condition occurs not rarely in animals, especially 
among the higher classes of vertebrates. Paul Gib has recently 
given the account of a bitch that always objected strongly to being 
shut up, and was greatly agitated during her seclusion, and that 
constantly after such treatment, but never otherwise, presented 
small quantities of glucose (up to 0.55 per cent.) in the urine. 

Such an effect of transitory emotions makes it difficult in many 
cases to determine the nature of an excretion of sugar both in man 
and in animals. Glycosuria following an attack of gall-stones (as 
observed by Finkler and Gans) may be caused by the simple irrita¬ 
tion of peripheral nerves, or by hyperemia of the liver; but it may 
also be the effect of the mere mental anguish of the patient during 
the painful, and possibly dangerous, passage of a gall-stone. Stu¬ 
dents of experimental pathology should bear in mind this possible 
cause of a transitory glycosuria of doubtful origin, and there is 


38 


DIABETES MELLITUS AND GLYCOSURIA. 


abundant evidence that it often occurs in laboratories, where the 
infliction of pain on animals is not always avoidable. Minkowski 
discovered glycosuria in 15 of 32 animals subjected to operative 
experiments, in which this phenomenon probably must be attrib¬ 
uted to mental influences. Examination of the figures given by 
Pavy, McDonnel, Seegen, Abeles, and others, for the quantity of 
sugar in the blood of the hepatic veins during experiments on ani¬ 
mals leads to the conclusion that the experiment increases the pro¬ 
duction of sugar in the liver through the mere suffering it causes. 
It is not at all improbable that the glycosuria that follows extirpa¬ 
tion of the salivary glands, so much expatiated upon by Reale and 
Rienzi, or that observed by Schiff after the ligation of the femoral 
artery, or by Minkowski after resection of the duodenum, as well 
as other slight and inconstant varieties of excretion of sugar in the 
urine, are to be referred to this category.* 

Bohm’s and Hoffmann’s “ Fesselungsglycosurie ” in the cat, sub¬ 
sequent to its being tied experimentally, is well known, and can be 
explained most easily by the mental state and emotion produced 
by such treatment, though asphyxia may also be operative in this 
instance. The same may be said of Velisch’s observation of gly¬ 
cosuria in the frog after tying it on its back, or after keeping it on 
its head in a narrow cylinder. 

In some cases nervous glycosuria may last for some length of 
time, but finally disappears. 

L, a medical student, works’hard at his books, and is alarmed now and 
then to find distinct reactions with the ordinary tests for sugar in his urine, 
which after rest and a trip to a warmer climate becomes normal. 

X, a youth of nineteen, was for several years addicted to masturbation, and 
every evening after dinner presented about 0.1 percent, of sugar, which dis¬ 
appeared some time after he reformed his ways. 

Mrs. T, now seventy-six years old, during middle age and after a period of 
great anxiety, excreted daily more or less than a gram of glucose with the 
urine. This caused her family some uneasiness, especially as a daughter 
had died of diabetes; but at present the old lady’s urine exhibits no trace of 
reaction two hours after an abundant mixed meal. 


* Falkenberg and Kiilz observed, after extirpation of the thyroid gland, glycosuria 
that was not constant, though it sometimes lasted for weeks. Naunyn, in his recently 
published monograph, probably correctly explains this glycosuria by the starvation con¬ 
sequent upon the operation. 




GLYCOSURIAS. 


39 


Count X Y Z, in a scientific controversy, both made and committed to paper 
a number of most absurd statements, for which he was subjected to severe 
but well-deserved criticism, by which he was greatly affected. During this 
time he availed himself of the opportunity to make some interesting investi¬ 
gations concerning the influence of emotion on metabolism, and on various 
occasions he found as much as 0.3 per cent, of glucose in his urine. After he 
had returned to the intellectual passivity for which nature evidently intended 
him, and time had consoled him for his disappointments, his urine returned to 
its natural condition. 

If, on the other hand, the nervous causes of glycosuria are pro¬ 
longed or become permanent, so will also the excretion of sugar 
with the urine, and this may continue for many years, and often for 
the rest of life. These habitual glycosurias have exactly the same 
etiology as true diabetes ; and there will be found to exist heredi¬ 
tary influences of a diabetic, a nervous, or a gouty nature, and the 
usual accidental influences : viz., painful emotions, intellectual 
overwork, sexual excesses, etc. 

Habitual glycosuria is found especially in persons suffering from 
those common functional disorders grouped under the name of 
neurasthenia, which disorders, when once they have appeared, 
seldom entirely leave the patient. 

Among neurasthenic patients, again, we may expect to find 
pathologic quantities of sugar in the urine, especially in cases com¬ 
plicated by gout or obesity ; and it is a matter of choice whether 
we ascribe the glycosuria to the neurasthenia or consider it a col¬ 
lateral symptom of the obesity or gout, which latter dystrophy, by 
the way, is accompanied with marvelous constant nervous symp¬ 
toms. Among obese persons we also not rarely find glycosuria, 
especially in those that exhibit neurasthenic stigmata. There is 
among the upper social classes a not rare type of middle-aged man, 
with a bodily weight as often above as below 200 pounds, with 
ruddy cheeks and a general appearance of health, but with high- 
strung nerves, great sensitiveness, and often with some slight gouty 
trouble.* If we adopt the rule of testing our patients’ urine an 


* As has already been mentioned, diabetes insipidus, like obesity and gout, may be 
converted into diabetes mellitus or it may be attended with the excretion of a small 
amount of sugar in the urine (Senator, Legroux). Such cases, however, seem to be quite 
rare, even comparatively. In the rare cases of recovery from diabetes mellitus a distinct 
diabetes insipidus sometimes remains. 




40 


DIABETES MELLITUS AND GLYCOSURIA. 


hour after dinner, we shall find in a large proportion of the repre¬ 
sentatives of the type described at least distinctly pathologic traces 
of sugar—simple glycosuria. In other cases we shall find a true, 
though mild, diabetes. 

Wherever we turn we often see in practice illustrations of the 
close relationship between all stages of the glycosuric dystrophy. 

In a family of eight children one sister died at twenty-nine in diabetic coma ; 
another, who subsequently died of carcinoma, developed the mild type of dia¬ 
betes when about fifty years of age; in a third, somewhat corpulent, but other¬ 
wise healthy, sister, I have, in the course of many years, found several times 
after meals from o. i to 0.2 per cent, of sugar in the urine. With the exception 
of the sister that died in coma, none of the family presents any nervous dis¬ 
order, but on the father’s side there are neuropathic individuals of closest 
relationship. 

In different branches of another well-known and widely spread family I 
have seen simple glycosuria, mild and severe diabetes, gout, and obesity, with 
or without traces of sugar. The psychopathic element in this in part highly 
intellectual family has manifested itself in fully developed psychoneuroses, in 
dipsomania, in perverted sexual desires, and in eccentricity. 

The son of a man who met his death by diabetic coma discovered in late 
middle age that he was excreting sugar, the condition being found to be one of 
slight simple glycosuria. The daughter of a woman who had presented slight 
glycosuria died in early life of severe diabetes, and so on. 

The daily excretion of sugar in the urine in cases of simple glyco¬ 
suria is always insignificant, and the amount is frequently so small 
that it can not with certainty be demonstrated in larger quantities 
of urine, even after abundant ingestion of carbohydrates. If in a 
sample of the urine collected during twenty-four hours a percentage 
of, for instance, 0.5 be found, the case can no longer be classed as 
one of simple glycosuria, unless special causes—such as excessive 
indulgence in alcohol, an acute infection, powerful emotion, and the 
like—have contributed to the condition. The quantity in small 
samples voided a certain time (from one to two hours) after meals 
varies from hundredths to tenths of a per cent., and may for'a little 
while, under the influence of agencies that increase the secretion, 
reach a somewhat higher figure. A percentage of 1.5, even in 
small quantities of urine, is rare in cases of simple glycosuria ; more 
than 2 per cent, scarcely occurs at all in an anomaly of this kind. 

Simple glycosuria causes of itself— i. e., by hyperglycemia and by 
loss of sugar—no symptoms at all or only ill-defined and transitory 


GLYCOSURIAS. 


41 


symptoms. We find in these cases, beyond the small quantities of 
glucose in the urine, usually no pathologic manifestations except 
the various neurasthenic stigmata and symptoms in lesser or greater 
number, and these can not possibly be ascribed to the insignificant 
deficiency in the power of assimilating carbohydrates or to the small 
addition to the normal quantity of sugar in the blood, which addition 
probably amounts to determinable quantities only for a compara¬ 
tively short part of the twenty-four hours. To avoid unnecessary 
repetitions, I refer to chapter iv for a consideration of those neuras¬ 
thenic symptoms, of which the most frequent and the most distress¬ 
ing are an excessive emotional irritability, insomnia, and enfeebled 
virility. I wish here only to remark that the glycosuria stands in 
no fixed relation to the intensity of the neurasthenic neurosis. We 
may find glycosuria present in cases of but slightly developed neu¬ 
rasthenia, and we may look in vain for it in cases in which many 
stigmata and symptoms combine to bring out in strong relief the 
neurasthenic picture which is scarcely ever complete in the indi¬ 
vidual case. 

The symptoms that may be caused by hyperglycemia and glycosuria in 
these cases are so vague that even a considerable experience and much atten¬ 
tion have not enabled me to arrive at definite conclusions with regard to some 
points. Pollakiuria, or increased frequency of micturition, even though the 
quantity of urine expelled at each voidance be small, is a usual, though not 
constant, symptom in cases of simple glycosuria. It is, however, common also 
in “ nervous ” patients without glycosuria, and it is often noticeable whenever 
the urine contains any great amount of crystals of calcium oxalate, which is 
often the case in the presence of simple glycosuria. 

I have found furunculosis in quite a number of cases, with such an insig¬ 
nificant excretion of sugar that I could not possibly class them among diabetics. 
Furunculosis is also one of the earliest symptoms of mild diabetes. With 
regard to furunculosis, also, we must remember the oxaluria so common in 
neurasthenic patients, and especially in those that show glycosuria. In the 
“idiopathic oxaluria” of Begbie, Cantani, and others, the clinical picture is 
made up of slight nervous and dystrophic symptoms, and among the latter the 
authors also name furunculosis. It is not improbable that other causes than 
hyperglycemia are here active, especially in view of the fact that furunculosis is 
much more frequent in mild than in severe cases of diabetes. 

Other cutaneous eruptions, especially eczema, are sometimes found in cases 
of simple glycosuria, which, like diabetes, frequently arise in persons with 
vasomotor irregularities of different kinds. It is difficult to assert any direct 
connection between these cutaneous troubles and glycosuria; they are both 
often found in cases of gout—a frequent disease in glycosuric individuals. 

4 


42 


DIABETES MELLITUS AND GLYCOSURIA. 


Patients aware of the presence of slight quantities of sugar in their urine 
sometimes mention dryness of the mouth or increased thirst, but the quantity 
of urine rarely exceeds 20 cu. cm. to the kilogram of body weight. 

The teeth, which in true diabetes are pretty certain to be carious and defec¬ 
tive after some years, are often in most excellent condition after decades of 
simple glycosuria. 

When the physician wishes to determine by careful investigation 
as far as possible the nature of a slight glycosuria, and to give it a 
name, he must fully understand that his task is entirely a practical 
one, and that he must give up all attempts to draw a distinct,, sci¬ 
entific limitation between simple glycosuria and diabetes. While 
bearing in mind that simple glycosuria and glycosuria in mild and 
severe cases of diabetes represent only a dystrophic symptom of 
various pathologic states and processes, we must remember that 
exactly the same gradual differences are to be observed in the excre¬ 
tion of sugar as in other dystrophic manifestations. What intelli¬ 
gent physician would undertake to determine where gout begins ? 
In obesity, which reveals itself to our senses much more readily 
than gout or diabetes, even the layman understands that the interval 
between the normal man and the representative of the highest 
degree of obesity may be filled by a thousand individuals in such a 
manner that only a minute difference exists between each man and 
his neighbor to the right and to the left in the long line. We meet 
with exactly analogous conditions in glycosuric patients. It is im¬ 
possible to decide precisely when the faint trace of sugar that, we 
must allow, may appear in normal urine ceases to be normal and 
passes over into simple pathologic glycosuria. It is equally im¬ 
possible to find the boundary-line between the latter and mild dia¬ 
betes, and in the chapter on metabolism we shall find that mild and 
severe “ forms” of diabetes are also connected by intermediate 
stages. The individual may sometimes, by slow degrees, and dur¬ 
ing a series of years, pass through all stages, from the normal state 
to that in which he is overtaken by death from diabetic coma. 
This, however, is not the usual course, and many patients remain 
in the vicinity of that place in the chain that they occupied a short 
time after the beginning of their dystrophy. Simple glycosuria, 
as already mentioned, often shows a decided tendency to remain 
unaltered for decades, in spite of all sorts of pernicious influences. 


GLYCOSURIAS. 


43 


Mild diabetes certainly not infrequently develops gradually from 
simple glycosuria, but it also often appears at once or after a short 
time as mild diabetes, and usually remains mild diabetes. If we 
can not deny that the severe type sometimes has gradually been 
evolved from the mild, it much more frequently shows itself in its 
severe character a short time after a normal state. 

In examining and forming an opinion on a case with a small 
amount of sugar in the urine, the physician must further always 
bear in mind that, as simple glycosuria may, under some temporary 
influence, momentarily resemble mild diabetes, so also may mild 
diabetes at times appear exactly like simple glycosuria, and that, 
consequently, repeated examinations are always necessary. Re¬ 
cently I examined two patients on the same day—Mrs. M. and 
Mr. R., both about forty years of age. An hour after a similar 
dinner of mixed food the urine of each contained fully o. 15 per 
cent, of glucose, although in the urine collected for the twenty-four 
hours there was a scarcely perceptible trace. The patients con¬ 
sumed 200 grams of cane-sugar each ; the urine in neither case 
afterward yielded a distinct reaction with Nylander’s solution, but 
in both cases reduced abundantly after boiling with a few drops of 
sulphuric acid.* In short, the two cases seemed for the moment 
to be as similar as they could be. They are, however, essentially 
different in nature. Mr. R. for fully ten years has exhibited a sim¬ 
ple, neurasthenic glycosuria, which during all this time, and with 
ordinary food, has appeared as it does now, without ever reaching 
considerable quantities of sugar or giving rise to diabetic symp¬ 
toms ; it will in all probability remain stationary in the future. 
Mrs. M. suffers from a true, though mild, diabetes of several years’ 
standing. A few weeks ago her urine contained over two per cent, 
of sugar, and there was some polyuria ; she has reached her present 
power of assimilation only after several weeks of strict diet. If she 
should for any length of time indulge in a free diet, which now was 
occasionally allowed for a couple of days for the sake of the experi¬ 
ment, her old symptoms would be certain to reappear. 

In other rare cases the same individual may, without any dififer- 


* In other words, neither urine contained glucose, but both urines contained some 
cane-sugar, which, after being inverted by boiling with acid, reduced (see below). 




44 


DIABETES MELLITUS AND GLYCOSURIA. 


ence in diet, and without any assignable cause, present a periodic 
alternation of simple glycosuria and true, though mild, diabetes. 

This is the condition that now and again is mentioned in medical 
literature as periodic diabetes. In the cases of this kind that have 
come under my observation a distinctly pathologic, though com¬ 
paratively insignificant, trace of glucose is found even during the 
“ free” intervals. Such a case is that of the Countess H., who has 
been under my observation for several years. The lady, who is 
somewhat over forty and very corpulent, shortly after her husband’s 
death began to suffer from constant thirst. The polydipsia excited 
the attention of the servants, and the family physician found con¬ 
siderable quantities of sugar in the urine. Since then, this most 
conscientious patient has for several years constantly adhered to 
the same diet, with a considerable reduction of carbohydrates (ioo 
grams of bread a day and some vegetables and animal food). Once 
or twice a year, at intervals of varying length, diabetic symptoms 
appear for some weeks, with the excretion of considerable amounts 
of sugar (from 20 to 25 grams daily), but these soon disappear, 
even if no change is made in the dietetic regimen. In the intervals 
the urine for twenty-four hours shows, with Nylander’s and 
Fehling’s solutions, just appreciable traces of sugar. At present 
the patient has just passed through a new diabetic period, which, 
unlike the previous attacks, continued for five months, until, when 
she appeared again in Carlsbad, I reduced for some time the carbo¬ 
hydrates to a minimum. The patient is now able to take eighty 
grams of bread daily, together with some vegetables, without show¬ 
ing more than traces of glucose in the urine, which will be ex¬ 
amined more frequently in order to effect without delay any reduc¬ 
tion in carbohydrates that may possibly be necessary. I consider 
it probable that the case will develop into a common, persistent, 
mild diabetes. 

Very likely similar cases, complicated by gout, have been designated “ dia¬ 
betes alternans" ever since the time of Peter Franks. By this appellation is 
generally meant a state in which alternately sugar and uric acid in abundant 
quantities appear in the urine. Gouty patients often present either simple glyco¬ 
suria or an especially mild diabetes. With the periodic increase in the power of 
assimilation, which may occur in such cases, the amount of sugar in the urine 
falls to a minimum. That a real alternation occurs, so that the quantity of uric 
acid increases as the quantity of sugar in the urine diminishes, and vice versa, 


GLYCOSURIAS. 


45 


is at any rate not proved, and among the large number of gouty and glycosuric 
patients that I have treated I have not been able to find a single case in which, 
as a result of the considerable analytic work necessary, the slightest evidence 
of such an alternation was detected. It is difficult to understand how the 
presence of uric acid in the urine should bear any fixed relation to the gly¬ 
cosuria. 

A connection between glycosuria and the presence of oxalic acid 
in the urine—the molecular construction of the latter giving it a 
position between glucose on the one hand, and water and carbonic 
acid on the other—has a good theoretic basis, and I have seen 
cases of simple glycosuria that, when free from glucose, have pre¬ 
sented marked oxaluria. 

Though no exact dividing-line can be drawn between adjacent 
cases of the one and the other, a comparison between the typical 
forms of simple glycosuria and of true though mild diabetes will 
show several practically important differences : 


Glycosuria. 

Smaller quantity of glucose which, even 
after abundant and protracted inges¬ 
tion of carbohydrates, seldom rises to 
any considerable fraction of one per 
cent, in the urine for twenty-four 
hours, and altogether only amounts to 
a very small number of grams. 

The excretion of glucose is in less definite 
relation to the amount of carbohydrate 
ingested. The patient may show 
some glycosuria after a hearty dinner, 
but may be capable of ingesting large 
quantities of cane-sugar or rice with¬ 
out glycosuria making its appearance, 
Emotions, alcohol, etc., have a very 
conspicuous influence in inducing gly¬ 
cosuria. 

The amount of glucose, therefore, under 
the same dietetic conditions, though 
always small, undergoes comparatively 
wide variations. 

Simple glycosuria gives rise to no distinct 
diabetic symptoms, except the patho¬ 
logic amount of sugar in the urine. 


Mild Diabetes. 

Larger quantity of glucose which, after 
abundant and protracted ingestion of 
carbohydrates, always reaches large 
fractions of one per cent., and usually 
more than one per cent, in the urine 
for twenty-four hours, the whole ex¬ 
cretion, under such circumstances, al¬ 
ways amounting to several grams. 

The excretion of glucose is in a more defi¬ 
nite relation to the amount of carbo¬ 
hydrate ingested, though it may be 
increased by emotional and other in¬ 
fluences. 


The amount of glucose under the same 
dietetic conditions usually varies less 
than in simple glycosuria. 

/ 

True diabetes, though mild, generally upon 
a free, mixed diet gives rise to other 
symptoms than glycosuria, especially 
to polydipsia and polyuria. 


46 


DIABETES MELLITUS AND GLYCOSURIA. 


Glycosuria. —( Continued.) 

Simple glycosuria has a more stationary 
tendency, and is often attended for 
decades with the same power of as¬ 
similating carbohydrates. 

After the ingestion of a large dose of some 
other saccharid than glucose, a certain 
amount of that saccharid appears in 
the urine, accompanied by no glucose 
or by a relatively small amount of it. 


Mild Diabetes.—( Continued .) 

True diabetes, even in its mild stage, has 
a more progressive tendency. The 
power of assimilating carbohydrates 
often gradually diminishes, and the 
mild stage not very rarely passes over 
into the severe stage. 

After a large dose of some other saccharid 
than glucose, a certain amount of glu¬ 
cose appears in the urine accompa¬ 
nied by no other saccharid or by a 
comparatively small amount of the 
ingested saccharid. 


The late excellent Norwegian physiologist and specialist in 
diabetes, Worm-Muller, considered that he had discovered a dis¬ 
tinct difference between glycosuria and diabetes in their different 
behavior after the ingestion of large amounts of other saccharids 
than glucose. In simple glycosuria, according to this observer, 
some part of a large amount of another saccharid ingested would 
pass unaltered in the urine, while in diabetes every trace of sac¬ 
charid found in this secretion appears in the form of glucose. 
Thus, in a case presenting pathologic excretion of glucose after the 
ingestion of from 200 to 300 grams of cane-sugar, one of three 
different conditions of the urine would arise : 


If cane-sugar only is found in the urine, the urine reduc- \ 

ing Fehling’s or Nylander’s solution not previously, { a diagnosis of glycosuria 
but only subsequently, to boiling with dilute sulphuric ( must be made, 

acid, / 

If both cane-sugar and glucose are found in the urine, 'k 

greater reduction taking place after than before boiling r a diagnosis °f gl>cosuria 
with dilute sulphuric acid,* ' must be made. 

If the urine contains only glucose, and the reduction is 'j 

as marked before as after boiling with dilute sulphuric f a diagnosis °f diabetes must 
acid, J be made - 


* I would remind the reader that in this experiment titration and not polarization 
must be used before and after boiling with dilute sulphuric acid. Before the boiling, 
the glucose alone reduces ; the cane-sugar does not. Both saccharids turn the polarized 
light to the right. By boiling, the cane-sugar is changed into “ invert sugar,” a mixture 
of levulose and glucose, of which the former turns the polarized ray of light to the left, 
while the latter turns it to the right, but both have about the same capacity for reduction 
(see below). 




GLYCOSURIAS. 


47 


This mode of distinguishing between diabetes and simple glyco¬ 
suria has, however, only relative value, and we find also in this 
respect only a gradual difference. In diabetes (except in some 
cases after long periods of abstinence from carbohydrates) glucose 
is far more easily made to appear in the urine after ingestion of 
cane-sugar than in simple glycosuria, and after certain amounts in 
the former only glucose may be found in the urine ; but after large 
amounts of cane-sugar even the diabetic patient of the most aggra¬ 
vated type may pass, in addition to large quantities of glucose, 
small quantities of unaltered cane-sugar. Minkowski found this 
to be the case even in diabetic dogs after the extirpation of the 
pancreas, though the dog—judging from many experiments re¬ 
corded in literature—is more prone than man to develop glycosuria 
after ingestion of cane-sugar. In several cases of slight simple 
glycosuria I have found the proportion between the amounts of 
cane-sugar and glucose excreted after the ingestion of large 
amounts of the former to vary greatly from one day to another in 
the same individual. In one case of simple glycosuria of long and 
stationary standing in a gouty and neurasthenic individual, the 
patient, to overcome his dread of diabetes, used once every year 
to take 300 grams of cane-sugar. The urine, which some time 
after every rich dinner contained, for a while, a small amount of 
glucose, after this enormous dose of cane-sugar yielded no distinct 
reaction with Nylander’s solution, although it contained a few 
grams of unaltered cane-sugar. One day, however, just after 
taking the 300 grams of cane-sugar, the patient got into a violent 
passion, and an hour afterward a small amount of urine contained 
1.3 per cent, of glucose, but only a small, doubtful amount of 
cane-sugar. The test being repeated some few days later, yielded 
the former usual result; the urine contained no definite amount of 
glucose, but a few grams of cane-sugar. 

Simple glycosuria does not perceptibly alter the “ patient’s ” state 
of nutrition, and generally shows a strong tendency to remain sta¬ 
tionary, even under the influence of deleterious circumstances. The 
later in life it appears, and the longer it has remained unaltered, the 
smaller is the danger of its development into true diabetes. When¬ 
ever gout exists as a complication, the probability of the glycosuria 


48 


DIABETES MELLITUS AND GLYCOSURIA. 


remaining unaltered is exceedingly great, and I consider such ex¬ 
cretions of sugar in the urine in elderly, gouty persons to be of 
small clinical importance ; but even an inconsiderable glycosuria, 
after having shown itself for a greater length of time, is most likely 
to continue through the patient’s whole life, and a development into 
true diabetes is not with certainty excluded. 

Hepatogenous Glycosuria .—The liver is the organ in which gly¬ 
cogen is stored as a reserve force, and the organ in which this 
glycogen is again converted into glucose and yielded up to the 
circulation for the purpose of generating energy by oxidation. It 
is evident, therefore, that certain disturbances in the activity of the 
liver may cause disturbances in the metabolism of the sugar of the 
blood, and occasion hyperglycemia and glycosuria. Though it 
involves some repetition, I consider it best, for the purpose of gain¬ 
ing a clear view of the subject, to make a summary of the different 
ways in which this may occur. 

The supply of glucose to the liver through the portal vein may 
be so large and so sudden that even a normal capacity of the liver 
to convert the surplus into glycogen is overtaxed, and the glucose 
over and above that which can be stored in the muscles and else¬ 
where, or be consumed in the tissues, enters the circulation. This 
is evidently the case in what we call alimentary glycosuria after 
very large amounts of glucose have been taken. Another instance 
of a similar form of glycosuria—which with Claude Bernard, who 
first demonstrated it, we may call alimentary, as its origin is essen¬ 
tially the same—is that produced by the injection into the mesen¬ 
teric veins or into the portal vein of glucose or glycogen (which is 
transformed into glucose in the blood). 

When hyperemia of the liver occurs, hyperglycemia may result 
from an increased production of sugar, either in consequence of the 
diastatic ferment of the blood attacking the glycogen more vigor¬ 
ously or of the liver-cells becoming more pronounced in their 
specific activity, including the secretion of sugar. It is certain that 
Bernard’s “piqure,” many kinds of poison, and most of those other 
conditions that induce glycosuria have been shown to be the cause 
also of hyperemia of the liver ; and that which directly causes hyper¬ 
emia of the liver, often causes also glycosuria. Arthaud and Butte 


GLYCOSURIAS. 


49 


have recently shown that after ligation of the splenic artery and the 
right gastro-epiploic artery, which considerably increases the supply 
of arterial blood of the liver, glycosuria arises. The finding by 
Exner (1898) of glycosuria in each of forty cases of gall-stones 
leads me to believe that the glycosuria also in these cases is due 
to the congestion of the liver. Trauma of the liver sometimes 
causes glycosuria—if through congestion or through nervous influ¬ 
ences is uncertain. Hyperglycemia and glycosuria also follow if 
arterial blood is injected into the hepatic artery (Pavy) or if the vaso¬ 
constrictor nerves of the liver are divided (Chauveau and Kauf- 
mann). On the other hand, anemia of the liver seems to induce 
hypoglycemia. After ligation of the hepatic artery Arthaud and 
Butte found at first hyperglycemia, probably brought on by the 
struggles of the animal during the experiment or by the loss of 100 
grams of blood taken before the application of the ligature for the 
sake of determining the quantity of sugar (see below); but after 
this transitory hyperglycemia, the ligation was followed by distinct 
hypoglycemia. Tangl and Harley also found hypoglycemia after 
ligation of the hepatic artery. 

Furthermore, glycosuria may arise from such disorders of circu¬ 
lation as prevent the blood in the abdominal vessels from passing in 
the portal vein through the liver in normal quantities, so that a 
large part of this blood escapes the customary regulating influence 
of the liver by being made to pass through the other otherwise com¬ 
paratively unimportant channels outside the liver. Claude Bernard 
thus caused glycosuria in the dog by ligation of the portal vein. 
Andral, as early as 1856, found sugar in the urine in a case of pyle- 
thrombosis, and Colrat and Couturier, in the seventies, confirmed 
this observation. 

Finally, we may not unreasonably assume that such processes 
as directly decrease the power of the liver to store the glycogen 
may tend to produce glycosuria, and some facts seem to corrobo¬ 
rate this. The retention of bile speedily empties the liver-cells of 
their glycogen (Dastre and Arthur, Hergenhahn), and Golowin 
found glycosuria after closure of biliary fistulae, v. Wittisch after 
ligation of the bile-ducts. Tscherinow observed glycosuria in asso¬ 
ciation with acute yellow atrophy of the liver, Schmitz with amyloid 
degeneration of the liver, Neusser with poisoning by phosphorus. 


50 


DIABETES MELLITUS AND GLYCOSURIA. 


(This effect of phosphorus, however, seems, according to Bollinger, 
Huber, and Miinzer, to be rather the exception than the rule.) 
Cirrhosis of the liver has been the subject of many investigations in 
this connection, but in default of an exact expression for the normal 
power of assimilation and of any considerable number of perfectly 
uniform researches, and on account of the frequency of excretion 
in the urine of small, pathologic amounts of glucose, apart from dis¬ 
ease of the liver, it is difficult to arrive at definite conclusions. I 
have in this connection observed a large number of patients with 
simple atrophic cirrhosis and some with hypertrophic cirrhosis of 
the liver, and repeatedly have found glycosuria, and sometimes true 
diabetes. On the other hand, I have seen quite a considerable 
number of patients in a far-advanced state of cirrhosis of the liver 
that were able to take large amounts of carbohydrates without de¬ 
veloping glycosuria, and I was for a long time unable to make up 
my mind as to the supposed intimate connections between cirrhosis 
of the liver and glycosuria. Even now I am able to accept such a 
connection rather on account of Naunyn’s figures of about sixteen 
per cent, of cirrhosis of the liver among diabetic patients than from 
my own experience. 

Naunyn’s observations seem to confirm Claude Bernard’s opin¬ 
ion as to the greater frequency of glycosuria in cases of incipient 
than in those of advanced cirrhosis. One sometimes, however, finds 
glycosuria in patients with most pronounced cirrhosis of the liver. 

Toxic glycosuria arises from the ingestion of various substances, 
and many experiments that have recently been made seem to indi¬ 
cate that almost any poisonous substance may increase the amount 
of sugar in the blood and cause glycosuria, and that this may even 
result through substances that are normally present in the blood, if 
they be injected or ingested in abnormally large amounts. 

Except in the cases in which phloridzin has been given, and in 
those of slow asphyxiation, the glycosuria that results from poison¬ 
ing is always caused by hyperglycemia, which may be the result of a 
toxic influence exerted in various ways. Such an occurrence may be 
brought about by a direct effect on the nervous centers, and through 
them on the vasomotor nerves, with hyperemia of the liver and in¬ 
creased production of sugar ; or by a paresis of the muscles, with 


GLYCOSURIAS. 


51 


decreased consumption of the sugar of the blood, either in conse¬ 
quence of metabolic changes in the muscles themselves, or in con¬ 
sequence of disturbances of respiration and want of oxidation ; or 
of an influence on the tissues and on cellular vitality, with deteriora¬ 
tion of the general metabolism ; or of some influence on the liver- 
cells, with a weakening of their power to store glycogen ; or of a 
change in the epithelial elements of the kidneys, in consequence of 
which they permit the escape of the sugar of the blood with the 
urine (phloridzin). We have as yet on this subject only hypotheses 
that are analogous to the theories concerning diabetes. An enor¬ 
mous amount of experimental work will be required to put us in 
possession of all the knowledge that is to be gained from a 
study of the glycosuria due to various forms of poisoning. 

In all of the glycosurias of this group, with the exception of 
that due to phloridzin, the amount of sugar in the urine keeps at a 
moderate level* and constitutes only an unimportant feature of the 
entire clinical picture. Having made its appearance with the other 
symptoms, the glycosuria generally persists for some time after the 
elimination of the poison. The glucose is often accompanied by 
other pathologic substances. One of these is lactic acid, which is 
considered to represent a station in the combustion of carbohy¬ 
drates on their way to complete oxidation and to the formation of 
carbonic acid and water. After the ingestion of chloralf or chloral- 
amid (Manchot), of nitrobenzol and nitrotoluol (Ewald, v. Mering, 
Magnus-Levy), of orthonitrophenyl-propionic acid (Hoppe-Seyler), 
side by side with the glucose we find the combined glycuronic 
acids, which reduce solutions of copper and bismuth and deflect 
the polarized light to the left, but do not undergo fermentation 
(see below). 

Acids , both without and within the organism, seem to favor the 


* Araki has recently induced glycosuria by the administration of veratrin, morphin, 
cocain, strychnin, amyl nitrate, and carbon dioxid, the amount of sugar in the urine 
reaching four per cent. There was often albuminuria. The lactic acid in the urine 
reached two per cent. 

| Ewald first saw reduction after ingestion of chloral, and attributed it to glucose. 
Von Mering, however, by the absence of fermentation, demonstrated the reducing sub¬ 
stance to be something else than glucose. It was found to be a combined glycuronic 
acid (urochloralic acid). In some cases both substances are present. 




52 


DIABETES MELLITUS AND GLYCOSURIA. 


molecular construction of sugar and to facilitate the transmutation 
of glycogen into glucose, just as alkalies seem to have the opposite 
effect.* If acids are introduced into the blood for some time and 
in sufficient quantities, they cause emaciation, anemia, lowering of 
temperature, neuralgia, paresis and paralysis, and, finally, a state 
that greatly resembles diabetic coma (Rolf, Walter, Hugonenq, 
Stadelmann, Kiilz, and others). Moreover, there may or may not 
be albuminuria. The glycosuria also is not constant, and when it 
follows, it is slight. It has been observed in cases of poisoning 
with sulphuric acid (Pavy), lactic acid (Golz, Naunyn), hydrochloric 
acid (Naunyn and others), salicylic acid (Pollatschek), prussic acid 
(Geppert), oxalic acid, orthonitrophenyl-propionic acid (Hoppe- 
Seyler), and the lower fatty acids (Mayer). 

Frerichs reports some cases of poisoning with sulphuric acid, in which he 
found sugar in the urine only exceptionally, though reducing substances, 
which do not undergo fermentation (combined glycuronic acids), are not 
rarely present. 

I. B. L., a healthy servant-girl of twenty-two, took a large quantity of con¬ 
centrated sulphuric acid and excreted as much as 0.5 per cent, of glucose 
(reduction, rotation, fermentation). The ^specific gravity of the urine was 
1.043, and no albumin was present. 

2. M. S., in the fifth month of pregnancy, drank, on May 26th, concentrated 
sulphuric acid; was given calcined magnesia in milk, but vomited blood; 
had violent pains in the mouth and throat, hoarse voice, and pain in the epi- 


* Acids cause saccharification of glycogen and starch, while alkalies do not. Coignard 
watered radishes, Martin-Damourette a vine, with alkaline water, and thus obtained a 
much smaller amount of sugar in the roots of the former and in the fruits of the latter, 
than by using ordinary water. Ehrlich found that frogs living in a solution of glucose 
stored a good deal of glycogen in their livers when sodium bicarbonate was added to the 
solution of glucose, but a comparatively small amount when acetic acid was added, Pavy 
assumes that sulphuric acid injected into the blood favors the transmutation of glycogen 
in the liver into sugar, but that injections of sodium bicarbonate favor its transmutation 
into something else. His opinion that the latter-named injections decrease the hepatic 
glycogen was not borne out by the experiments of Kiilz, which yielded exactly opposite 
results. In cases of severe diabetes with large quantities of (diacetic and /Foxybutyric) 
acids in the blood the hepatic glycogen is distinctly diminished (Frerichs, v. Mering and 
Minkowski, Stadelmann). As a result of his experiments Kiilz reached the somewhat 
uncertain conclusion that dextronic acid, sugar acid, and mucous acid contribute to the 
formation of glycogen in the liver. This seemed certainly to be the case with the an- 
hydrid of glycuronic acid, which is molecularly closely related to glucose. Even if all 
these weak acids should in some way contribute to the formation of glycogen in the liver, 
it can scarcely be doubted that stronger acids in the blood are decidedly antagonistic to 
such a result. 



GLYCOSURIAS. 


53 


gastrium. She voided 700 cu. cm. urine of a specific gravity of 1.045 ( 0 > free 
from albumin, sugar, and other reducing substances. On May 28th the spe¬ 
cific gravity was 1.039, the next day 1.031, and free from abnormal substances. 
On June 1st the urine had a specific gravity of 1.034, was dark, smelt of ace¬ 
tone, and yielded a wine-red reaction with ferric chlorid (diacetic acid from 
inanition). There was no reduction, no rotation of the polarized light, no 
albumin. The sulphuric acid present in the urine equaled 1.68 grams, of which 
1.43 were mineral sulphates and 0.25 aromatic sulphates. Thus, the latter 
were increased, although the whole amount was not abnormal. The vomit¬ 
ing and the pains continued, so that only small quantities of liquid food 
could be taken during the first few days. On June 3d the patient was able 
to take more food; on June 5th the wine-red reaction of the urine had dis¬ 
appeared, while the specific gravity was 1.010, and the sulphuric acid equaled 
1.18 grams. 

It has been proved that a large number of partly indifferent, 
partly poisonous, metals and metallic salts , when injected into the 
blood or taken by the mouth, are capable of causing glycosuria. 
This is the case with injections into the blood of ordinary sea-salt 
(Bock and Hoffmann, see below), sodium bicarbonate (Kiilz, Kess¬ 
ler), sodium acetate, sodium valerianate, sodium succinate, sodium 
phosphate, and sodium sulphate (Kiilz, Kuntzel), as well as with 
sodium salicylate taken by the mouth (Burton). 

Phosphorus (Bollinger, Huber, v. Jaksch), arsenic (Bernard, 
Quinquaud, Saikowski, Masoin), mercury (Reynoso, Rosenbach, 
Bouchard, Cartier, v. Mering), lead (Brunelle, Strauss), urqnium 
(Cartier), also cause glycosuria more or less constantly. 

At least under some of the conditions named the hypergly¬ 
cemia is induced through the agency of the nerves, as glycosuria 
does not follow the injection of sea-salt if the splanchnic nerves are 
divided (Kiilz). 

Phosphorus causes glycosuria, lactaciduria, and peptonuria, but none of these 
is constant. Von Jaksch observed glycosuria in 15 of 43 cases of phosphorus¬ 
poisoning. Of Miinzer’s ten cases, of which several terminated fatally, it is in 
most cases especially stated that the urine contained no sugar, and in no single 
case is it mentioned that there was any. Laub in two cases noted 0.15-0.7 P er 
cent, of glucose. Von Jaksch mentions that glycosuria is common in such 
cases when icterus is present. 

Arsenic, which has the power of preventing glycosuria after Bernard’s punc¬ 
ture, and is used therapeutically because of its property of diminishing the ex¬ 
cretion of sugar in the urine, in toxic doses sometimes causes glycosuria. 
Whether this is a consequence of the glycogen being driven out of the liver 
and the muscles being unable to consume the increased sugar in the blood 


54 


DIABETES MELLITUS AND GLYCOSURIA. 


(Zimmer), or the effect of the accumulation of arsenic in the brain (Scolozoboff), 
has not been decided. 

Feilchenfeld has described a case of acute arsenical poisoning with an ex¬ 
tensive, fully developed, multiple neuritis. The case, which first seemed to be 
one of true diabetes (4.7 per cent, of sugar), soon settled down to an insignifi¬ 
cant glycosuria. 

Both sugar and albumin are sometimes found in the urine of persons under¬ 
going antisyphilitic mercurial treatment, but only when the mercurial poisoning 
is pronounced (Frerichs, Kussmaul, Lewin). Graf noticed in rabbits constant 
glycosuria after doses of mercuric chlorid. 

Brunelle found from 0.2 to 1 per cent, of glucose in the urine after 
administration of 200 grams of syrup in more than half of a number of cases 
of lead-poisoning. 

Uranium and its salts constantly cause glycosuria and albuminuria.* 
Those that, not very wisely, have introduced uranium nitrate into therapeutics 
for the purpose of diminishing glycosuria, should have first considered its 
poisonous properties. Cartier found subcutaneous injections of from ]/ 2 to 2 
milligrams per kilo of body weight to be fatal, the animals (rabbits) mani¬ 
festing thirst, diarrhea or constipation, loss of appetite, somnolence, torpor, 
paresis or paralysis, retarded respiration, emaciation, lowering of temperature, 
and death in coma, with or without convulsions. The glycosuria appeared about 
twenty minutes after the injection, reached its maximum in a day or two, seldom 
exceeded more than 1 per cent, of sugar, and then decreased. The urine first 
increased, then decreased, anuria finally setting in. Acetone was present, 
probably from inanition. The autopsy disclosed a severe congestion of the 
whole gastrointestinal tract, with ulcerations in the stomach and the duodenum. 
The liver was intensely hyperemic ; large amounts of the drug caused cellular 
necrosis. The kidneys were also markedly congested, and the seat of diffuse 
parenchymatous inflammation, often with cellular necrosis. The heart pre¬ 
sented subendocardial ecchymoses. Neither the nervous system nor the pan¬ 
creas nor the lungs presented noticeable changes. 

Alcohol , which in small amounts increases the power of assimilat¬ 
ing carbohydrates, has in large amounts the opposite effect. Thus, 
the diabetic is, after generous indulgence in alcohol, found to 
excrete far more sugar than he does otherwise with the same 
allowance of carbohydrates in his diet. Simple glycosuria may, 
under the same influence, be attended with such quantities of sugar 
in the urine as are common in diabetes ; while a normal individual 
may, after excesses “in Baccho,” present glycosuria. This effect 
is more easily brought about in some persons than in others, but 


* Glycosuria following the ingestion of uranium was first observed by Leconte in the 
beginning of the fifties; then by Gmelin, Bernard, Blake, Rabuteau, Curee, Chittenden, 
Kowalewski, Whitehouse, Lambert, Woroschilski, and Cartier. 




GLYCOSURIAS. 


55 


probably may be caused in any individual—a fact well worth know¬ 
ing and remembering, to avoid false diagnoses of diabetes. Bever¬ 
ages that contain large quantities of both alcohol and carbohy¬ 
drates are especially efficient in causing glycosuria, which is often 
observed after indulgence in champagne and beer and also in that 
disgusting mixture of arrack, sugar, and water, which is called 
Swedish punch, and often flows too freely in my native country. 
The glycosuria following the use of alcohol is generally moderate, 
and the sugar in the urine keeps within one per cent., but after 
excessive indulgence may continue for several days, especially 
appearing after meals. 

In cases of chronic alcoholism one also sometimes finds a small 
amount of sugar in the urine. I have, however, seen a consider¬ 
able number of such persons with a normal power of assimilating 
carbohydrates. 

Ether , now and again, causes glycosuria, whether injected in the veins 
(especially the portal vein, Harley), inhaled, or taken by the mouth. There 
are, however, individuals that, in spite of long and great abuse of ether, 
exhibit no glycosuria (Frerichs). Andral observed diabetes in such a case, but 
the question whether post or propter remains undecided. 

Chloroform often causes the excretion of small amounts of sugar (Eulen- 
burg and others). 

Chloral causes the appearance in the urine of urochloralic acid, belonging to 
the group of combined glycuronic acids (v. Mering); on account of its reducing 
properties this acid has often been mistaken for glucose. Chloral, however, 
now and again also causes true glycosuria (Telz, Ritter, Eckhard). Manchot 
observed slight glycosuria in about one-fourth of a number of cases in which 
chlorala 7 nid was being administered. 

Amyl nitrite * causes glycosuria more surely than alcohol, ether, chloroform, 
or chloral, the sugar in the urine rising at times above two per cent., and 
appearing for twenty-four hours after inhalation (Fr. A. Hoffmann). Bouchard 
thinks this due to the transmutation of the oxyhemoglobin into methemoglobin 
and to deficient oxidation; others lay stress on the vasoparalytic influence and 
the congestion of the liver. 

Lactic acid is under these circumstances, as under others, sometimes found 
in the urine in association with glucose. 

Ammonia, when injected into the portal vein, causes glycosuria, which also 
Bouchard ascribes to the decreased capacity of the blood to absorb oxygen. 

Glycosuria from Asphyxia .—As early as 1868 Senator, in the 
course of his investigations on the effects of disturbed respiration, 


*Siebold, “ Ueber d. Amylnitrit-Diabetes,” Diss., Marburg, 1874. 




56 


DIABETES MELLITUS AND GLYCOSURIA. 


found glycosuria to be one of these effects, although it proved 
subsequently, after continued clinical observation, to be the excep¬ 
tion rather than the rule. 

Senff in 1869 observed that dogs, after inhaling carbonic acid, 
constantly exhibited glycosuria, sometimes accompanied by albumi¬ 
nuria. He found hyperglycemia, but a normal capacity on the 
part of the muscles to consume sugar, and he therefore attributed 
the hyperglycemia to an increased production of sugar in the 
liver. 

Dastre in 1879, * n hi s thesis “ Sur la Glycaemie Asphyctique,” 
made a distinction between slow and rapid asphyxiation : the former 
causing hypoglycemia, the latter hyperglycemia, and both, glycosu¬ 
ria. In slow asphyxiation, when the animals breathed in closed 
compartments or in rarefied air, the amount of sugar in the blood 
was distinctly diminished, and Dastre attributes the glycosuria 
under these conditions to the want of oxygen and the greatly re¬ 
duced oxidation, in consequence of which even the decreased 
amount of sugar in the blood is not consumed. 

In the nineties Hoppe-Seyler’s pupils—Araki, Zillesen, and 
Irisawa—proved that different conditions and circumstances that 
induce dyspnea or are attended with a deficiency in the supply 
of oxygen (agony, severe anemia, etc.), often also cause glucose 
and lactic acid to appear in the urine, though neither the one nor 
the other is always present. 

Hoppe-Seyler’s pupils consider the glycosuria attending the col¬ 
lapse due to many poisons (curare, delphinin, strychnin, morphin, 
chloroform, ether, sulphonal, carbonic acid, hydrocyanic acid, etc.), 
as well as that appearing during tetanus, after epileptic attacks and 
other similar states, as being of asphyctic type. Schiff, Sauer, and 
others also insist that the glycosuria does not appear, or that it 
disappears, if asphyxia is prevented by proper artificial respiration. 
Still there are other plausible explanations : Dastre is of opinion 
that asphyctic blood excites the liver to increased production 
of sugar, and remarks that the glycosuria due to many poisons 
appears before any deficiency of oxidation could be effective. 

Glycosuria due to carbon monoxid was mentioned by Bernard 
(1857)* investigated by Senff (1869), and afterward studied by 
Richardson, Ollivier, Biefel and Pollek, Frerichs, Hasse, Kahler, 


GLYCOSURIAS. 


57 


v. Jaksch, Araki, Garofalo, Rosenstein, Walter Straub, Vamossy, 
and others. It is caused by hyperglycemia ; the sugar in the urine 
may reach 1.5 per cent, in man (Frerichs) and 4 per cent, in the 
dog (Senff). Lactic acid injected subcutaneously reappears almost 
entirely in the urine, but sugar injected does not. In fact, Walter 
Straub, Rosenstein, and Vamossy all have arrived at the conclusion 
that the amount of glucose in the urine in this most remarkable 
kind of glycosuria is not increased by the ingestion of sugar, and 
that the glucose is not derived from carbohydrates, but from pro- 
teids, especially fibrin (Vamossy). 

Curare causes glycosuria, as was known to Bernard, and the condition 
has since been made the subject of many investigations.* The glycosuria 
appears quickly, and is associated not only with polyuria, but also with hyper¬ 
secretion of the sudoriparous, salivary, lacrimal, and intestinal glands. The 
abdominal organs, especially the liver, are intensely hyperemic. Langendorff 
maintains that extirpation of the liver does not prevent the glycosuria due to 
curare, although starvation does. Unlike what takes place in the glycosuria 
due to strychnin, the liver afterward may contain a considerable amount of 
glycogen. Schiff, Penzoldt, Fleischer, Zuntz, and Sauer agree as to the free¬ 
dom of the urine from sugar, if artificial respiration is properly maintained. 
As long as this is successful, the urine contains a reducing, but not a ferment¬ 
ing, substance (probably pyrocatechin, Sauer), but as soon as respiration begins 
to fail sugar appears.* The glycosuria due to methyl delphinin seems to be 
very like that due to curare. 

Glycosuria due to strychnin was observed in the fifties by Claude Bernard 
and by Schiff; it was afterward studied by Langendorff and by Giirtler. It is 
most easily induced in frogs in the autumn, when their livers are well stored 
with glycogen. The sugar is somewhat slow to appear, and may not do so for 
a whole day. It may then persist for several days, although at a low figure. 
The liver is emptied of its glycogen (the “ paraplasma ” or substratum, for it is 
diminished), and the hepatic cells are reduced in size and become polygonal 
in shape (Langendorff). Extirpation of the liver prevents the development of 
the glycosuria, as does also destruction of the spinal cord, while severance of 
the head from the body does not (Claude Bernard). The glycosuria does not 
depend on the tetanus, as it appears also if the muscles are entirely paralyzed. 
There is some polyuria and lactaciduria. 

Morphin gives rise to glycosuria, as is well known from Eckhard’s work, and 
as can easily be demonstrated by injecting from three to five centigrams 
of the sulphate or hydrochlorate subcutaneously in a rabbit. The sugar ap¬ 
pears in small quantities as early as the second hour after the injection, and 
often persists only for a few hours; the condition is the result of hyperglyce- 


* Winogradoff, Casal, Lionville, Langendorff, Voisin, Saikowski, Schiff, Dock, Gag- 
lio, Demant, Penzoldt and Fleischer, Zuntz, Sauer (“ Pfliiger’s Archiv,” 1S91). 

5 




58 


DIABETES MELLITUS AND GLYCOSURIA. 


mia (Seegen). Like the glycosuria after Bernard’s puncture, that due to mor- 
phin is prevented not by section of the pneumogastric, but by that of the 
splanchnic nerves or of the spinal cord above the roots of these nerves. After 
large doses the transitory polyuria is followed by a decreased secretion or even 
by anuria. An injection of glycerin prevents the glycosuria (Luchsinger), or 
at least has an effect in that direction (Eckhard). 

Sugar is sometimes found in the urine of morphinists and sometimes not 
(Pichon). I have found only slight traces in a few cases of this kind. In these, 
as in other cases of poisoning, the acute state is attended with more pro¬ 
nounced glycosuria, and more frequently, than the chronic state. 

Veratrin causes slight glycosuria and lactaciduria (Araki)—not in conse¬ 
quence of diminished “ glycolytic power ” on the part of the blood, but on ac¬ 
count of an increased production of sugar, according to Lepine. 

Von Noorden observed glycosuria after the use of ergotin. 

Many diuretics cause glycosuria. This and some other facts have of late led 
some observers to the conclusion that there is a glycosuria due to polyuria. 
When Bock and Hoffmann injected a one per cent, solution of sodium 
chlorid into the veins of the rabbit, the animals first presented distinct poly¬ 
uria and later glycosuria.* Jacoby (Strassburg) found that sulphocaffeinic 
acid, sodium caffein, benzoate, and theobromin-sodium salicylate (“ diuretin ”), 
all diuretics, caused glycosuria.f 

Klemperer, who strongly maintains that glycosuria may result from poly¬ 
uria, found sugar after administration of digitalis. We often find inosite ac¬ 
companying polyuria—why not also glucose ? There are also, at times, cases 
of diabetes insipidus with traces of glucose in the urine—though this does not 
at all seem to be a common occurrence. It is not easy to make up one’s mind 
definitely as to the glycosuria resulting from polyuria. The facts already 
mentioned may be explained in different ways, and there is one important and 
well-known fact that denotes that polyuria does not always produce glycosu¬ 
ria. Cirrhosis of the kidneys is attended with polyuria, but not with glycosu¬ 
ria, and in case of diabetes it has a decided influence in decreasing the 
glycosuria. 

Some animal poisons cause glycosuria. Ewald, and afterward Strauss, found 
as much as six per cent, of glucose in the urine after administration of thy- 
roidin ; when the thyroidin ceased, the glycosuria also ceased. 

Teschemacher noted glycosuria after injections of Koch’s tuberculin; 
Dufresne, after injections of pancreatin. 

Toepfer and Freund observed glucose after injections of a dialysate of 
feces. The fact that the glycosuria reached a greater intensity and was of 


* This experiment, however, has many other effects than polyuria, and especially a 
decrease in the glycogen in the liver, and hyperglycemia. In some cases there was also 
albumin and even blood in the urine, denoting a condition of the kidneys that by some 
persons is considered conducive to glycosuria. 

t Neumann administered “ diuretin ” in a case of insufficiency of the aortic valve, and 
observed polyuria and glycosuria, which he ascribes to the heart-disease. The glyco¬ 
suria may as well have been caused by the “ diuretin.” 


I 




GLYCOSURIAS. 


59 


longer duration when feces from diabetics were used than when the feces were 
derived from healthy individuals, may, if not dependent on mere chance, be 
explained by the customary greater abundance of the products of the putre¬ 
faction of proteids in the intestines of diabetics. The theory advanced by 
Toepfer belongs, in my opinion, to what Punch calls “things one would 
rather have left unsaid.” 

As is well known, the liver is supposed, among other functions, to have that 
of retaining poisonous substances absorbed from the alimentary canal and of 
preventing their entrance into the blood. On the other hand, the toxicity of 
the urine is an index of the amount of such substances in the blood. Roger 
(“Action d. Foie sur les Poisons,” Paris, 1887) observed that patients suffering 
from various hepatic disorders and secreting a highly poisonous urine readily 
developed glycosuria after the ingestion of considerable amounts of sugar; and 
he expresses the opinion that the liver has in those cases lost in part its capacity 
for retaining the poisons and for converting alimentary sugar into glycogen. 

Phloridzin-glycosiiria .—Scarcely had Koninck (1885) discovered 
phloridzin when v. Mering (1886) observed that this substance 
causes an exceedingly peculiar form of glycosuria. 

Phloridzin is a glucosid obtained from the bark of the root of 
certain species of Pyrus and Prunus. It crystallizes in glistening 
silky crystals and is easily soluble in warm water, but requires 1000 
parts of cold water for its solution. Phloridzin is levogyrate. It is 
decomposed by boiling with diluted acids : 

C 2 i H 24 °io 4 " H 2 0 = C 6 H 12 0 6 + C15H14O5. 

Phloridzin X Water = Phlorose + Phloretin. 

Phlorose, as will be seen, is a hexose, has the same molecular 
construction as glucose, which it resembles greatly, is dextrogyrate, 
and reduces, though in less degree than glucose. 

Phloretin, though less efficient in this respect than phloridzin, also 
causes abundant glycosuria. Treated with caustic alkali, it forms 
phloretic acid (an aromatic alcoholic acid) and phloroglucin (a tri- 
atomic aromatic alcohol), both of which are probably also formed 
in the organisms ; they do not cause glycosuria, but increase the 
combined aromatic sulphatic acids in the urine (Moritz and Prauss- 
nitz). In the course of the intoxication, and as long as the glyco¬ 
suria lasts, there appears in the urine a brownish-violet coloration 
on addition of ferric perchlorid (due to phloridzin). With phlore¬ 
tin a similar, but more deeply violet, reaction is obtained. The 
urine, especially if the animal has been kept fasting, becomes 
slightly albuminous. 


6o 


DIABETES MELLITUS AND GLYCOSURIA. 


The glycosuria commences after a couple of hours, after o.oi 
gram per kilo of body weight has been given by subcutaneous injec¬ 
tion, and after double that dose by the mouth in dogs. After large 
doses the amount of sugar may rise to more than thirteen per 
cent. (Moritz and Praussnitz), or even to more than eighteen per 
cent. (v. Mering) in dogs, and it may persist for several days or a 
week (Coolen). The quantity of urine is not increased, but the 
specific gravity may rise to 1.070. In rabbits the glycosuria is 
less marked and more transitory, but it appears regularly after 
subcutaneous injections ; after injection of two grams it persists for 
from seven to twenty hours (Lusk).. It is also observed in the 
hen, the goose, and the frog (Ritter and Cremer). It has been 
observed in the goose after extirpation of the liver (v. Mering, 
Thiel). 

The organism, even under the influence of phloridzin, assimilates 
a considerable part of the ingested carbohydrates. The larger the 
dose of phloridzin, the greater the absolute value of the sugar in 
the urine, but the smaller its value in relation to the dose. 

Klemperer, and recently (1899) Achard and Delamare, have 
found phloridzin to give rise to much less marked glycosuria in 
cases of chronic nephritis than otherwise. 

Phloridzin, as may be understood from the relation between the 
quantity ingested and the amount of sugar in the urine, acts in a 
“ specific ” manner, and not by reason of being a glucosid, as other 
glucosids do not cause glycosuria (v. Mering, Gley, Germain See). 
Thus, 6 grams of phloridzin, containing 2.5 grams of phlorose, 
may cause glycosuria with 41.7 grams of sugar in the urine. 

An abundant mixed diet, including a great deal of sugar and 
starch, causes the glycosuria to reach its maximum ; but it continues 
during starvation and even after extirpation of the liver. Von Mering 
found glycosuria in the dog when the liver and the muscles were 
almost, but, as Kiilz remarks, not completely, emptied of glycogen. 

When the food is made up exclusively of fat, the glycosuria falls 
as low as in starvation (v. Mering, Moritz, and Praussnitz)—a most 
remarkable circumstance, which speaks against the opinion of those 
who think that fat may, with a deficiency of carbohydrates and 
of albumin, form glucose in the organism. 

As long as the food is abundant enough to cover the heat-wants 


GLYCOSURIAS. 


6 I 


of the organism and the loss of sugar in the urine, even large doses 
of phloridzin do not cause any general disturbances ; but during 
starvation and poisoning with phloridzin inanition speedily develops ; 
the animals quickly lose weight; the proteids of the organism are 
decomposed; acetone, diacetic acid, and /2-oxybutyric acid show them¬ 
selves in the urine, while the ammonia increases, and weakness and 
somnolence become manifest. If the animals are then killed, the 
liver and the muscles are found in a state of fatty degeneration. 
[Rosenfeld is of the opinion that the fat in the liver in these cases 
is derived from an infiltration of fat from other parts than the liver, 
and not from fatty degeneration of proteids in the liver-cells.] If 
the animals are given food and the phloridzin is withheld, they 
speedily return to health. The liver is said to store more glycogen 
from meat under the influence of phloridzin than if the animals 
receive only sugar. 

The most peculiar feature of the phloridzin glycosuria, however, 
is the presence of a decreased percentage of sugar in the blood. 
Von Mering and almost all other observers agree on this point.* 

Von Mering found from 0.075 to 0.09 per cent, of sugar in the 
blood with from 6.5 to 9.2 per cent, of sugar in the urine of the 
dog, the blood normally containing about o. 10 per cent. Gabrit- 
schewski found that, while the white corpuscles of hyperglycemic 
(diabetic) blood contain an abnormally large quantity of glycogen, 
they contain an unusually small amount thereof in phloridzin cases. 

There are only two ways of explaining phloridzin-glycosuria—it 
may arise in consequence of some alteration in the epithelial ele¬ 
ments of the kidneys (v. Mering), or it may be the result of some 
combination of phloridzin or one of its derivatives with glucose 
(Graham, Lusk). In either case the passage of the latter into the 
urine is facilitated, and the blood, the liver, the muscles, and the 
whole organism are thus deprived of both sugar and glycogen, 
which are constantly renewed, though not at the same rate as they 
are lost. 

After extirpation of the kidneys the hypoglycemia ceases, but 


*Pavy, whose researches on blood-sugar have led him to such curious conclusions, 
has not found any hypoglycemia during phloridzin-glycosuria (“ Journ. of Physiol.,” 
London, 1894). Coolen also found no decrease of blood-sugar, and Levene found a 
somewhat higher figure for the sugar in the renal vein than in the arterial system. 



62 


DIABETES MELLITUS AND GLYCOSURIA. 


hyperglycemia does not arise. Zuntz took the urine from both 
ureters of the dog immediately after an injection of phloridzin into 
one of the renal arteries, and found that the urine on this side 
immediately became sacchariferous, while that on the other side 
became so only when the phloridzin had reached the kidney on 
this latter side through the entire circulatory system. 

According to Cornevin, phloridzin has an analogous influence on 
the lactogenous glands and increases the lactose in the milk. 

Antipyrin (See and Gley) and syzygium jambolanum (Graser) 
act in a manner opposite to phloridzin, and diminish the glycosuria. 

Phloridzin and phloretin are sometimes used for the purpose of 
simulating diabetes. 

The glycosuria due to infections diseases is generally attended with 
the presence of insignificant quantities of sugar in the urine, and 
occurs very inconstantly in the course of acute exanthematous and 
other infections. It is not yet known under what conditions and 
during which period the sugar appears. On the one hand, we 
know positively that the sugar in the urine in diabetes or glyco¬ 
suria decreases and sometimes disappears during the febrile state, 
while, on the other hand, the infectious diseases attended with fever 
often induce glycosuria. Poli recently, after the administration of 
glucose in cases of scarlet fever, diphtheria, septicemia, tonsillitis, 
and pneumonia, found a decreased power of assimilation and a 
much greater portion of the ingested glucose in the urine than 
would have appeared in normal individuals. In cases of malignant 
pustule Roger found the sugar in the blood in the beginning of the 
disease normal, or even somewhat below the customary amount; 
then a moderate hyperglycemia, with from 0.22 to 0.30 per cent, of 
sugar in the blood appeared, and after death the liver contained no 
glycogen. In other cases of febrile disease the glycosuria appears 
during the period of defervescence and the beginning of the con¬ 
valescence. I have also seen it during the prodromal stage, and it 
does not seem to be excluded from any stage of febrile infections. 

Glycosuria is often found in the course of, and after, influenza 
and malaria; and it is also observed in the course of typhoid fever 
(Seyfert, Bordier), diphtheria (Frerichs), scarlet fever (Redon, 
Zinn), measles (Fischer, Bouchut, Bordier, Barlow, Gelmo), dysen- 


GLYCOSURIAS. 


63 


tery (Anstoots), cholera (Heintz, Samoje, Huppert, Gubler, v. 
Terray, Vas, and Gara), croup, pertussis, pneumonia (Bordier, 
Semmola, Stern, Beale, Reynoso), erythema nodosum (Bordier), 
variola, and vaccinia (during the florid stage, Gueneau, Prevost), 
anthrax (Proust, Philipeaux, Vulpian, Charcot, Frerichs, Goolden), 
lyssa (Eichhorst), lymphangitis, and erysipelas (Redard), and septic 
processes (Poli). 

It would seem as if all suppurative processes might induce glyco¬ 
suria, which has several times been observed in association with 
gangrene, phlegmon, noma, and especially with furunculosis and 
carbuncle. Wagner was, I believe, the first to mention glycosuria as 
complicating these two latter skin diseases. Still, as is well known, 
furuncles and carbuncles are common manifestations of diabetes. 
Furuncles especially appear at an early stage of the dystrophy, and 
there still remains some doubt if, in the cases in which they have 
been considered to be the cause of glycosuria, they have not really 
been the effect of a mild diabetes. 

In rare cases syphilis causes glycosuria or real diabetes by attack¬ 
ing either of the organs that preside over the metabolism of carbo¬ 
hydrates. In most such cases arteriosclerosis, cerebral softening, 
hemorrhage, or gummata in the brain precede the appearance of 
the glycosuria. The few cases that I have seen were examples of 
glycosuria or mild diabetes. Sometimes their syphilitic nature be¬ 
comes apparent e juvantibus , and quite a number are recorded of 
cure by antisyphilitic treatment. Decker has reported such a case 
in which the sugar appeared a little more than a year after the in¬ 
fection. Whether syphilis can cause glycosuria in any other way 
than through lesions of the brain, the liver, or the pancreas, is not 
known.* 

The prognosis of glycosuria (or diabetes) due to infectious dis¬ 
ease is decidedly more favorable than that due to any other cause— 
the sugar generally disappearing from the urine after or during con¬ 
valescence. On the other hand, some infections undoubtedly may 
lead to true diabetes ; but even in such cases one may sometimes 


* One writer has affirmed—in a book and in advertisements on the walls in Carlsbad— 
that he cures diabetes, which he considers almost always to be an effect of syphilitic in¬ 
fection, either acquired or inherited, perhaps from some ancestor of the dark ages. Such 
a statement must not be taken too seriously —quid verbis affirniat satis est verbis negare. 




64 


DIABETES MELLITUS AND GLYCOSURIA. 


observe instances of perfect recovery. I have seen this take place 
after typhoid fever and after influenza, and Zinn mentions a similar 
occurrence after scarlet fever, and Burdel in three cases after 
malarial fever. 

In cases of cholera the sugar appears chiefly in the abundant urine follow¬ 
ing the anuria ; it is often accompanied by indoxyl and albumin ; the sugar 
rarely amounts to one per cent, and disappears during the first days of conva¬ 
lescence. Cases of true and even of severe diabetes are also observed in con¬ 
nection with cholera (Frerichs); but sugar is far from being found in all cases. 
Von Terray, Vas, and Gara found it only in one case of sixteen ; the glyco¬ 
suria began twelve days after the end of the anuria ; the sugar rose to 0.5 per 
cent, and persisted for three days. The urine of several other patients 
strongly reduced copper, but did not deflect the ray of polarized light, and did 
not undergo fermentation. 

In cases of typhoid fever it seems that sugar may appear in the urine as early 
as during the prodromal period. A clergyman came to Carlsbad for some dys¬ 
peptic trouble, and presented slight evening elevation of temperature and felt 
generally ill. A dull note on percussion over the apex of the left lung led me to 
suspect an incipient tuberculosis. A large specimen of urine was found to 
contain 1.1 per cent, of glucose. I quickly sent the patient to his home, where 
the typical temperature-curve of typhoid fever developed. After the end of 
the typhoid (or before) the glycosuria disappeared. 

Malaria is not rarely accompanied by transitory glycosuria, which comes 
on after every paroxysm and sometimes, though rarely, may develop into true 
diabetes.* The glycosuria diminishes or disappears under the influence of 
quinin. Burdel found sugar in 14 per cent, of cases of quartan or tertian 
type, in 22 per cent, of cases of quotidian type, in 28 per cent, of cases of per¬ 
nicious malaria, and in 80 per cent, of cases of malarial cachexia. He has 
recorded three cases of a distinctly diabetic nature, in which perfect recovery 
ensued after the use of quinin. 

Since influenza , in the beginning of the nineties, again invaded the civilized 
world there have been published many observations of glycosuria or diabetes 
arising in the course of this disease, really much more dreadful than dreaded. 
I have myself seen all forms of defective power of assimilating carbohydrates 
during and after an attack of influenza, most of the cases presenting slight 
degrees of glycosuria. In other cases of simple glycosuria that I have had 
under observation for many years, repeated and severe attacks of influenza 
have been without any effect whatever on the glycosuria. I have seen several 
cases of diabetes following influenza improve greatly after convalescence from 


* Peter Frank and Sydenham, more than a century ago, mentioned diabetes in con¬ 
nection with malaria. Burdel, in 1859, directed the attention of the profession to the 
small quantities of sugar in the urine of patients suffering from malaria. Several French 
physicians in North Africa (Calmette, Range, Duponchet) have contributed to the litera¬ 
ture on this subject. In “ Malaria and Diabetes,” Diss., Rostock, 1896, Otto Jacobson 
gives the bibliography. 



GLYCOSURIAS. 65 

the causal disease, and I have seen at least one case in which perfect recovery 
ensued. 

Mr. X., a Finlander, some thirty years old, came in June, 1890, to Carls¬ 
bad, having had his first attack of influenza half a year before. In February 
he had had another severe attack, with high fever, violent pains in the back 
and legs, and great prostration. Early during convalescence the patient began 
all at once, on a certain day, to drink and to urinate freely, and an apothecary 
found in the urine a large amount of glucose, which by a specialist was esti¬ 
mated at 8.8 per cent. Unfortunately, I could obtain no information as to 
whether any diacetic acid had been present. The patient consulted Prof. 
Holsti, who affirmed the existence of diabetes mellitus, prescribed a strict diet, 
and after some time sent the patient to me in Carlsbad. The general state of 
health was then much improved, and there were no diabetic symptoms. A gen¬ 
erous amount of carbohydrates was allowed and, no glycosuria appearing, 
the amount was slowly increased until it reached at least 300 grams a day. 
The urine remained free from glucose, nor could that substance be found after 
administration of 200 grams of cane-sugar. For some time after the patient’s 
arrival at home he continued to be free from glycosuria upon ordinary diet, 
but I know nothing of his subsequent fate. 

In this, as in some other cases, I have no doubt the glycosuria was due to 
the influenza. 

Blot, in 1850, found in the urine of pregnant women a variety of 
sugar that Hofmeister afterward proved to be lactose. This puer¬ 
peral lactosuria begins during the last months of pregnancy and 
persists throughout the whole period of lactation, during the begin¬ 
ning of which it seems to be most pronounced, so that it may reach 
two per cent. Abeles found lactose in every one of 30 cases ; Ney 
observed it exceptionally before parturition, but in 80 per cent, of 
the cases he detected it from two to four days after parturition.* 
Lemaire found in the urine quite small quantities of glucose and 
isomaltose before parturition, and lactose only after parturition, but 
in large quantities. 

There is no doubt that pregnancy and childbirth sometimes give 
rise to true glycosuria. Puerperal glycosuria is much rarer than 
puerperal lactosuria. I have seen one patient who, after some 
months following parturition, was sent to Carlsbad with a diagnosis 
of diabetes. The urine contained small quantities of a dextrogy¬ 
rate-reducing substance, which readily underwent fermentation and 
disappeared in the presence of common yeast. I am unable to 


* See, besides, the treatises of Sinety, Kirsten, Spiegelberg, Johannowski, Hofmeister, 
Kaltenbach, and others. 





66 


DIABETES MELLITUS AND GLYCOSURIA. 


state how long this glycosuria lasted, but after two years the urine, 
with an ordinary free diet, contained no glucose. Marcus men¬ 
tions glycosuria up to 0.7 per cent, during pregnancy; Rossa 
found glucose during the seventh month, and Lang found that 
pregnancy is quite often attended with some loss of the power of 
assimilating carbohydrates. 

Sometimes parturition is followed by true diabetes. 

The saccharid often found in the urine of nursing infants is lac¬ 
tose (Poliak, Eichhorst), which passes into the urine more easily than 
other kinds of sugar. 

Cl. Bernard found sugar in the amniotic liquor in animals, observed later also 
by Moriggia and by Cramer. The amniotic fluid contains the urine of the 
fetus, and this fetal glycosuria, like the glycosuria of hibernating animals, 
constitutes one of the best arguments of those who see in hyperglycemia and 
glycosuria the effect of deficient combustion in the muscles ; but sugar in the 
amniotic liquor does not seem to be at all a constant phenomenon in normal 
women, and it is sometimes absent even when diabetes exists in the mother 
(Williams, Naunyn), though, like other liquids of the organism, it may in other 
cases of diabetes contain quite considerable (up to 0.7 per cent.) quantities of 
glucose (Husband). Fetal glycosuria and the glycosuria of hibernates deserve 
further investigation. 

Obesity and Glycosuria .—About one-third of all diabetic patients 
are corpulent; and very fat persons, according to several observers, 
present more frequently than others pathologic traces of sugar in 
their urine. I have, in several instances, found that persons who 
in early middle age suddenly grew corpulent at the same time be¬ 
gan to exhibit distinct traces of sugar for a short while after 
meals, the urine having previously, under similar circumstances and 
with the same tests, proved to be normal. Almost all fat people 
with glycosuria present also neurasthenic symptoms. Some of 
these patients eventually develop true diabetes, but generally 
remain in the mild stage. Still, obesity is no safeguard against 
severe diabetes even exclusive of pancreatic cases; the severe dys¬ 
trophy, however, within a short time puts an end to the obesity. 
Kisch believes that in about fifty per cent, of cases of hereditary, 
and in about fifteen per cent, of acquired, obesity pathologic excre¬ 
tion of sugar takes place sooner or later. The first of these 
figures appears to me somewhat too high. 


GLYCOSURIAS. 


67 


Gout and Glycosuria .—Gout is more often than any other disease 
associated with glycosuria or diabetes. Any physician with many 
gouty patients under his care will, if he adopt the practice of testing 
at least once the after-dinner urine of every patient for sugar, 
find that a large percentage of gouty individuals excrete for some 
time every day distinctly pathologic quantities of glucose. This 
glycosuria may set in before the appearance of gouty symptoms, 
which when mild are often for years overlooked both by patient 
and physician ; in other cases the urine remains normal for some 
time after the appearance of distinct gouty symptoms. In all such 
cases neurasthenic symptoms seem to be present. Whether gout 
or glycosuria has been first to make its appearance, no fact is of 
better prognostic import in a case of glycosuria than its association 
with gout. In almost all of the many cases of this kind that I have 
seen the glycosuric dystrophy has shown a strong tendency to 
remain stationary, and often, for the important purpose of encour¬ 
agement, I tell such patients that they will never die until somebody 
clubs them, which rarely fails to make their faces brighten with the 
most intense satisfaction. 

Diabetes Insipidus and Glycosuria .—Over and above polydipsia and poly¬ 
uria as effects of hyperglycemia, we may explain a connection between dia¬ 
betes mellitus and diabetes insipidus by the close proximity of the centers for 
glycosuria and polyuria on the floor of the fourth ventricle. The existence of a 
separate center for polyuria (and polydipsia)— i. e., diabetes insipidus—also ex¬ 
plains why neither the intensity nor the degree of the glycosuria has any fixed re¬ 
lation to the degree of the polyuria. One patient may pass in the twenty-four hours 
1.5 liters of urine containing forty grams of glucose, while another may with the 
same amount of carbohydrates and other food pass in the same time three liters 
of urine with twenty grams of glucose. Many think, with Klemperer, that poly¬ 
uria per se, by its influence on the kidneys, favors the elimination of glucose 
with the urine, as it favors the elimination of inosite. Sometimes, though 
rarely, one therefore finds small quantities of sugar, which are too insignificant 
to constitute diabetes mellitus in a case of distinct diabetes insipidus (Mann- 
kopff, Senator). 

Starvation and Glycosuria .—Claude Bernard observed that dogs, 
after having been subjected to starvation, on again receiving carbo¬ 
hydrates presented glycosuria. Lehman (1873) and Hofmeister 
(“Arch. f. exp. Path.,” 1887) have made investigations in this field. 
A dog, weighing two kilos, showed, after some days of abstinence 


68 


DIABETES MELLITUS AND GLYCOSURIA. 


from food, distinct glycosuria after the ingestion of as little as ten 
grams of starch. The sugar under such conditions appeared one 
to two hours after meals, and generally persisted for only a few 
hours in small quantities, although sometimes it reached nearly four 
per cent. In their normal state the animals generally were able to 
receive about five grams of glucose per kilo of body weight with¬ 
out presenting glycosuria; after starvation the sugar appeared in the 
urine after less than two grams per kilo of body weight, the rapidity 
of absorption from the alimentary canal being, in the latter case, 
rather diminished than increased. It is to be remembered that 
starvation undoubtedly plays some part in the etiology of true 
diabetes. 

Fatigue and Glycosuria. —Zimmer and others have observed that 
muscular exercises up to a certain point, in addition to their cus¬ 
tomary healthful influence on diabetic patients, also have a tendency 
to diminish existing glycosuria ; but too long walks, too much phy¬ 
sical effort of any kind has a contrary effect; and sometimes severe 
fatigue is followed by a considerable increase in the amount of sugar 
in the urine. The same influences will sometimes show themselves 
in normal persons, so that after muscular excesses glycosuria may 
appear for a short while and quickly disappear after rest. 

Cold and Glycosuria. —Bohm was, I think, the first to mention 
the slight glycosuria that may come on after exposure to cold ; it 
has since been observed by Araki and others in rabbits and dogs 
after application of ice around the body. Exposure to severe cold 
is not rarely mentioned by diabetic patients themselves as a proba¬ 
ble cause of their dystrophy. 

Senility and Glycosuria. —Small quantities of sugar often appear 
in the urine of old persons. This senile glycosuria is of no clinical 
importance, and entails upon the physician no other duty than to 
withhold the fact from the “patient,” who might be unnecessarily 
alarmed by such an information. 

Cachexia or Marasmus and Glycosuria. —In cases of carcinoma, 
tuberculosis, Addison’s disease (Burghardt), leukemia (Rebitzer),and 
in other diseases that are accompanied by marked cachexia or maras- 


GLYCOSURIAS. 69 

mus, slight traces of glucose are often found in the urine (Zimmer and 
others). On the other hand, it is often observed that the glyco¬ 
suria perceptibly diminishes in cases of diabetes as a cachectic or 
marantic state develops (Naunyn and others). 

The Kidneys and Glycosuria .—It is well known that the same 
amount of hyperglycemia may cause in different persons a widely 
different degree of glycosuria (see Seegen’s figures), and there is a 
wide-spread opinion that the kidneys have an influence on the latter 
(Lepine and others). This opinion seems corroborated by several 
recently acquired facts, which I recapitulate here. 

The glycosuria due to phloridzin seems to depend upon changes 
in the kidneys. We know that after extirpation of the pancreas in 
birds, whose normal glycemia is about 0.14 or 0.15 per cent. 
(Kausch), the hyperglycemia reaches a higher figure than in mam¬ 
mals before glycosuria sets in ; or, in other terms, that the kidneys 
of birds have a greater power of preventing the sugar of the blood 
from passing over into the urine (Kausch). Klemperer found, in 
nephritis, glycosuria (of 0.35 per cent.) with a normal quantity of 
sugar in the blood. Other changes in the kidneys seem also to 
bring about a diminished power of retaining the sugar of the blood. 
Frerichs, Morison, Habershon, and Pavy (cited by Naunyn) saw 
chyluria associated with glycosuria. Naunyn found sugar in con¬ 
junction with hemorrhages from the kidneys. Jacobi found that 
diuretics (theobromin, sulphocaffeinic acid, “ diuretin ”) cause gly¬ 
cosuria, which seems easily brought about in traces when polyuria 
exists from any cause whatever— e. g., diabetes insipidus. Most of 
these facts, however, may be explained in other ways, and “renal 
glycosuria” at the present moment represents scarcely more than 
a hypothesis. 


7 ° 


DIABETES MELLITUS AND GLYCOSURIA. 


CHAPTER IV.—SYMPTOMS AND COMPLICATIONS OF 
MILD AND SEVERE DIABETES. 

Diabetes mellitus is, as already mentioned, not a disease or a 
clinical entity, but a syndrome that may arise from a number of 
quite different processes in the organism. The glycosuria is not 
necessarily the first in the series of manifestations that mark the 
change in the patient’s state of health. 

In the great majority of cases the precursory signs that are not 
rarely observed are referable to the nervous system and belong to 
the neurasthenic group. When a patient, with a urine still free 
from sugar and with nothing more abnormal than perhaps the 
presence of a rather large quantity of crystals of calcium oxalate, 
has for some time complained of insomnia, irritability, enfeebled 
sexual power, neuralgia, etc., glycosuria may appear and slowly 
progress. In other less frequent cases changes in the vessels, new- 
growths, cerebral softening, hemorrhages, parasites, or traumatic 
influences may cause cerebral symptoms before glycosuria makes 
itself manifest. 

In still other cases, and especially in persons that are approach¬ 
ing middle age, I have several times found that the first appearance 
of sugar in the urine was preceded by a tendency to corpulence, 
whereupon a simple glycosuria or a mild diabetes has set in. 

In rare cases it is possible, before glycosuria begins, to diagnos¬ 
ticate disease of the pancreas, then generally of carcinomatous 
nature. 

Upon the whole, a rule prevails—though one with many excep¬ 
tions—that a diabetes that afterward pursues a mild course quite 
imperceptibly invades the patient, and years may pass after the first 
appearance of sugar in the urine before an accidental analysis, a 
slowly increasing polydipsia, a poor and complicated healing- 
process, or some local complication direct the patient’s or the phy¬ 
sician’s suspicions on the right track. Many physicians omit the 
important investigation of the urine, and it often happens that the 
specialist— e. g., the ophthalmologist or the dermatologist—fore¬ 
stalls the family physician in discovering the existence of diabetes. 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 71 

In other cases, especially in such as prove to be of a severe kind, 
diabetes sets in suddenly with marked glycosuria and specific 
diabetic symptoms, without any prodromal manifestations. 

Mild, slowly developing diabetes is much more common than 
severe diabetes. 

When the secondary dystrophy, the general disturbance of nutri¬ 
tion, has developed in consequence of the primary lesion of the 
nervous system, or the pancreas, etc., the effects may be induced 
in any organ as a result of either the deficiency on the part of the 
organism to fully utilize its carbohydrates and its consequent inani¬ 
tion, or of the action of certain toxins, or from defective central or 
peripheral nervous influences. 

Among the toxins in the blood we include the superfluous amount 
of sugar contained therein. In mild cases this probably is the only 
toxin, and one whose deleterious influence has been enormously 
overrated. A glycemia of o. I 5 per cent, may still be considered 
not in excess of the normal; above 0.4 per cent, is found only in a 
small minority of cases of diabetes (Seegen, Naunyn, and others). 
Persons suffering from true diabetes, who can not be persuaded to 
adhere strictly to a proper diet and who constantly present glyco¬ 
suria (and hyperglycemia) may live in fairly good health for more 
than twenty years. This single fact proves that hyperglycemia per se 
can not possibly be a very powerful nocens. Its worst effect is prob¬ 
ably the retaining firmer than is the normal the water in the blood¬ 
vessels, and thus, to a certain extent, desiccating the tissues. This 
causes some disturbance in the nutritive state and the functional 
power of the organs ; it may, e. g., bring about cataract and con¬ 
tribute to the development of gangrene, suppuration, and other dis¬ 
integrating processes, or of neuritis and other “parenchymatous” 
changes. The hyperglycemia may also be in part responsible for 
the diabetic endarteritis and the arteriosclerosis. The hyperglyce¬ 
mia, however, which in most cases is quite moderate, generally 
takes a very long time to bring about these changes. 

A much more deleterious effect is attributable to the acid toxins, 
the free fatty acids, the diacetic acid, and the /5-oxybutyric acid. 
When the physician sees for the first time a diabetic patient, the 
quickest and best way of determining approximately the stage of 
the diabetic dystrophy is to make use of Gerhardt’s test, which 


72 


DIABETES MELLITUS AND GLYCOSURIA. 


consists in pouring a few drops of ferric chlorid in a tube nearly 
filled with the patient’s urine. The appearance of a beautiful wine- 
purple color denotes directly the presence in the urine of diacetic 
acid, and indirectly often the presence of that most ominous sub¬ 
stance, / 3 -oxybutyric acid (see below). It may then be concluded 
that the patient is in the severe stage of diabetes, that he has at 
the utmost only a few years of life left, which will pass in a struggle 
with the autophagy and the acid diathesis (“acidosis ”), with all its 
manifold dangers, and that death will probably be caused by the 
blood-toxins. 

What role each of the different pathologic factors—the toxins 
and the deficient nervous influences, etc.—play in the production 
of anatomic lesions is only imperfectly known. A good deal of 
mystery surrounds especially the purely nervous “ trophic ” influ¬ 
ence and its anomalies in diabetes as in other dystrophies. 

In this chapter will be considered dystrophic general changes 
and those that occur in each of the different organs. However 
wide a clinical difference may exist between a diabetic patient in 
the mild and one in the severe stage, there is no distinct scientific 
demarcation separating these two stages, and it is injudicious to 
contribute to the idea prevailing in some quarters of two entirely 
different “forms” of diabetes. I give, therefore, no separate 
description of mild and severe diabetes, but only point out the toxic 
and cachectic nature, and the autophagy of the latter, and describe 
its usual final scene—diabetic coma. 

In connection with the clinical symptoms, we must consider the 
pathologic anatomic lesions of diabetes. These are often but little 
marked, both macroscopically and microscopically. After the 
existence of mild diabetes, which is not per se fatal, changes of a 
purely diabetic character are generally overshadowed at the autopsy 
by alterations due to the intercurrent or complicating disease. 
After diabetes in the severe stage or of long standing, the autopsy 
is certainly very likely to reveal characteristic changes. These, 
however, even when found in those organs that play a role in the 
pathogenesis of diabetes,—the nervous system, the pancreas, and 
the liver,—are far more frequently an effect than a cause of the 
diabetes, and represent retrogressive and degenerative processes 
due to the marasmus and the cachexia. The alterations in the 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


73 


kidneys, the most frequent of all, have no connection with the 
origin of the dystrophy, but are the results of its effects on the 
renal functions. 

SPECIFIC DIABETIC AND DYSTROPHIC SYMPTOMS. 

The sugar that appears in the urine in cases of simple glycosuria 
is present in determinable quantities only for some time after meals, 
while in cases of true diabetes, however mild, it is present under 
continued ordinary diet throughout the whole or, at least, the 
greater part of the twenty-four hours, being absent only when the 
patient’s stomach is empty just before meals, and especially in the 
morning before breakfast. With restriction of the carbohydrates 
to a quantity below the patient’s power of assimilation, the sugar 
in the mild stage of the dystrophy disappears from the urine. In 
the severe stage, when glycosuria is derived at least partly from 
proteids, the urine constantly contains glucose—except, perhaps, 
just before death, when the entire metabolism fails. 

After carbohydrates have been taken glycosuria begins in about 
half an hour, and so quickly reaches its maximum that the greater 
part of the sugar in the urine may have been excreted during the 
first hour. The whole excretion generally does not last more than 
five or six hours, and often a shorter time. In rare cases one some¬ 
times finds a distinct postponement of the whole excretion. 

The glycosuria following proteids in the severe stage of the dys¬ 
trophy is attended with the excretion of less sugar, and reaches 
its maximum later than after ingestion of carbohydrates ; or, in 
other words, the glycosuric curve due to proteids shows a lower 
wave. 

The intensity of the glycosuria— i. e ., the amount of glucose ex¬ 
creted in twenty-four hours—varies greatly, and depends on the 
power of assimilation and on the quality and quantity of the food 
ingested. In cases of true diabetes, however, after prolonged free 
diet it generally reaches a considerable degree and always some 
number of grams. Anything below one, or even two, grams under 
such circumstances is properly considered simple glycosuria. 
Sometimes the glycosuria reaches quite extraordinary figures, and 
it may reach one kilo, in twenty-four hours. Dickinson found in 
6 


7 4 


DIABETES MELLITUS AND GLYCOSURIA. 


one case 1500 grams, and some French observers have noted still 
higher figures. 

The intensity of the glycosuria — i. e ., the percentage of glucose — 
varies exceedingly during the twenty-four hours. The minimum is 
always found in the morning before the patient’s first meal, and a 
large number of diabetics present at this time of day no glycosuria 
that is discoverable with our ordinary tests. The maximum is 
generally reached between one and two hours after meals, and there 
are usually three distinct waves during the twenty-four hours, their 
height depending on the nature of the food. With a strict diet no 
reaction may be observed in mild cases or only a slight one. 
In advanced cases, with a liberal supply of carbohydrates we some¬ 
times find ten per cent, of sugar. Naunyn noted eleven per 
cent. Higgins and Ogden speak of twenty per cent. (?) Urine 
containing more than six per cent, of sugar is rare. In the course 
of an enormous number of analyses I have found some few show 
more than nine per cent., but only one reaching ten per cent. 
The percentage of glucose, depending under all circumstances 
largely on the quantity and quality of the food, forms in itself only 
a vague expression of the intensity of the diabetic dystrophy.* 

A patient living exclusively on meat and fat (water and salts), 
with 0.3 per cent, of glucose in his urine, is much worse off than 
another living on an abundant ordinary mixed diet, with three per 
cent, of glucose in his urine. The same patient who, one or two 
hours after dinner, exhibits three per cent, of sugar in his urine, 
may early the next morning exhibit only 0.05 per cent. When I 
hear of any one whose urine contains from three to five or seven 
per cent, of glucose, I conclude that he is diabetic—nothing more ; 
but if I hear of some one whose urine contains 0.5 per cent, of glu¬ 
cose, I gain scarcely any information at all about his case—it may be 
one of simple glycosuria, or of mild or severe diabetes. When I 
hear of any one whose urine contains 0.5 per cent, of glucose, 


* Bouchard unconditionally and sans phrase proposes to designate as severe every case 
of diabetes with an excretion of over fifty grams of glucose in the twenty-four hours ; and 
as mild, every case with less than this amount. This is for me a most striking illustration 
of the possibility of complete absences intellectuelles , even in men of genius. Many a 
diabetic patient may, according to this most extraordinary classification, repeatedly be a 
severe case on Mondays and a mild one on Tuesdays, and vice versa. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 


75 


with strict diet, this at once tells me that he is in the severe stage. 
It is useless to give figures of the glycosuria without some infor¬ 
mation as to the diet. 

With an exclusive diet of meat and fat, glycosuria, which dis¬ 
appears entirely in the mild diabetic stage, rarely reaches above 
two or three per cent, in the severe stage. 

In severe cases the patient often passes a clear, pale, greenish- 
yellow urine with a specific gravity that often is nearer 1.040 than 
1.030, and that sometimes may reach far above the first figure. 
Several observers mention 1.070; Proust and Bouchard, 1.074. 
Diabetic urine, however, especially in mild cases, varies enor¬ 
mously in appearance, specific gravity, and other qualities. A dia¬ 
betic in the mild stage, when he has not received carbohydrates 
beyond his limit of assimilation, passes urine that, besides being 
free from glucose, is otherwise scarcely different from that which 
a healthy person passes under the same dietetic conditions. We 
quite frequently find, even in severe cases, a urine of perfectly nor¬ 
mal, sometimes even a somewhat high, yellow color, and in mild 
cases not rarely a strong sediment of uric acid. Under the micro¬ 
scope the conditions often are normal, although sometimes there 
may be a rather large amount of the small crystals of calcium oxal¬ 
ate and sometimes also occasionally hyaline and more rarely 
granular casts. The nitric-acid test not uncommonly discloses 
the presence of albumin, and the colored zone above the acid 
is frequently pronounced. By reason of the abundance of animal 
food the urea and other derivatives of proteids are generally pres¬ 
ent in rather large quantities, and the specific gravity, therefore, is 
often high, even when no sugar is present. In many cases in the 
mild stage, however, the specific gravity is below 1.030, and not 
only within normal but within very common limits.* One may 
find urines of a specific gravity of 1.020 that contain quite a con¬ 
siderable amount (above one per cent.) of glucose. Sometimes 
one may even find distinctly pathologic, though small, quantities 
of glucose in urine of an exceptionally low specific gravity. Some 


* A normal middle-aged man, who eats much meat, often passes urine of a specific 
gravity nearer 1.030 than 1.020. One may sometimes, apart from diabetes, even find 
the urine of comparatively normal persons with quite a high specific gravity. Only re¬ 
cently I encountered a specific gravity of 1.034 in such a case. 




76 


DIABETES MELLITUS AND GLYCOSURIA. 


time ago I saw a urine of 1.005 specific gravity undergo a beauti¬ 
ful reduction with Nylander’s and Fehling’s solutions before, but 
not after, fermentation. It came from a gouty patient with simple 
glycosuria, who had been on a spree and had drunk two quarts of 
beer. True, though mild, diabetes may give rise to exactly such a 
urine either after prolonged abstinence from carbohydrates or dur¬ 
ing one of those periods, sometimes observed in mild cases, when 
the power of assimilation becomes very high or, finally, when some 
care in diet has been observed, but much water has been drunk. 

It is interesting to note the differences in view as to the fre¬ 
quency of albuminuria in association with diabetes. Schmitz noted 
albuminuria in 68.6 per cent. (!?),* Bouchard in 43 per cent., 
v. Dusch in 25 per cent., Garrod in 10 per cent, of their cases of 
diabetes. Grube (1878) states that he found albumin in the urine 
in 191 of 473 cases of diabetes, or in 40 per cent. In the severe 
stage of the disease albuminuria is much more frequent than in the 
mild stage. Including all cases of true diabetes in private practice, 
it will be found that Grube’s figures, which certainly are rather too 
high than too low, best represent the truth, while in hospitals, 
where chiefly severe cases are found, the figures will be consider¬ 
ably higher (see below). 

In some cases the solution of ferric chlorid shows the presence 
of diacetic acid (Gerhardt’s most important reaction), which, except 
with inanition, is absent in mild cases. 

For the other changes in diabetic urine I refer the reader to the 
chapter on Metabolism. 

Increased thirst , polydipsia , and polyuria are, as is well known, 
frequent symptoms of diabetes, and hold a causal relation with 
each other, which is still far from perfectly understood. Thirst 
and polydipsia are certainly causes of polyuria, and any one, 
whether diabetic or not, who drinks much, will pass a large quan¬ 
tity of urine. The increased thirst of diabetes must arise from the 
increased amount of sugar in the blood, which keeps the water in 
the vessels firmer than normal, and dries the tissues, which still are 
thirsting when a normal quantity of water is ingested, just as they 


* These figures can scarcely be explained in any otherjway than by the zone of urates 
(with Heller’s test) having been mistaken for one of albumin. 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 77 

may hunger from the loss of glucose and from the protoplasmic 
disintegration (see below) with a normal supply of food. Hyper¬ 
glycemia in itself acts on the kidneys as a diuretic. When enor¬ 
mous doses of saccharids are given, the urine always suddenly 
increases.* To some extent an increased want of water arises 
within the organism merely in consequence of the carbohydrates 
passing off as glucose instead of being oxidized into water and car¬ 
bonic acid. If the supply of carbohydrates in the food is restricted 
and hyperglycemia and glycosuria cease, polydipsia and polyuria 
often also cease. 

Polyuria may, however, arise also in consequence of direct vaso¬ 
motor influences, and not be the effect but the cause of increased 
thirst and polydipsia. Thus, lesion of the “ lobus hydruricus ” in 
the vermis, near the seat for Bernard’s puncture, causes diabetes 
insipidus, as does also lesion of Kahler’s centers. Further, the in¬ 
creased excretion of urine is observed in progressive paralysis. 
These facts suffice to explain, easily, cases of diabetes mellitus with 
slight glycosuria and marked polyuria, and cases of diabetes insipi¬ 
dus with slight traces of sugar, and the circumstance that the poly¬ 
uria sometimes remains after the disappearance of the glycosuria in 
the rare cases of incomplete recovery from diabetes mellitus. 

Sometimes cirrhosis of the kidneys contributes to the polyuria 
and polydipsia of diabetes mellitus ; in these cases, often of a gouty 
nature, the sugar in the urine, from some unknown cause, usually 
decreases as the cirrhosis advances. 

Pick mentions that ingested water passes through the kidneys in 
a shorter time in diabetics than in normal persons. 

The quantity of urine is generally increased only moderately—to 
two or three liters. More than five liters is rare, except in hospital 
practice with almost exclusively severe cases. Sometimes enormous 
quantities are observed. Dobson noted 14, Cantani also 14, Fiir- 
bringer 17 liters ; Schindler mentions 16 liters in a child, etc. 
Such quantities always belong to the most severe cases. 

Increased thirst, polydipsia and polyuria do not, however, consti¬ 
tute such constant symptoms as many members of the medical pro- 


* The frequency of the pulse decreases, but the systolic and diastolic excursions of 
the heart become greater (Vespa). 




78 


DIABETES MELLITUS AND GLYCOSURIA. 


fession seem to think. In the severe stage, especially regardless 
of diet, this group of symptoms is certainly, as a general thing, 
quite pronounced. In the mild stage, even apart from diet, the 
quantity of urine often keeps within the normal, and the condition 
corresponds with what already Peter Frank has called diabetes decip- 
iens. Even a moderate restriction of carbohydrates will in this 
stage keep the quantity of urine within normal limits in about 
fifty per cent, of the cases. Sometimes diabetic patients may pass 
even an exceptionally small quantity of urine in the twenty-four 
hours. I have observed cases in which only goo, 800, and 700 
cu. cm. were passed. 

I have records of 65 diabetic patients, whose urine has been measured 
for the twenty-four hours during a somewhat considerable time, and find 
that of 27 in the severe stage, 22 have generally passed more, and 5 less, 
than 1600 cu. cm.; and that of 38 mild cases, half the number have passed 
less, the other half more, than this quantity. All of these patients were of high 
stature, and include Scandinavians, Britons, Germans, and Americans. On 
the other hand, it may be conceded that almost all the possible errors in meas¬ 
uring have contributed to make the figures too low; and that in many cases 
the diet has corrected a preexisting polyuria. 

As the quantity of glucose, so also the quantity of urine, is gen¬ 
erally larger during the day than during the night; but the rule 
has many exceptions, both glycosuria and polyuria depending on 
the character of the food. Thus, when the largest meal, dinner, is 
taken late in the evening, the urine and the glucose often reach 
higher figures during the night than during the day. Increased 
intensity of glycosuria is, as a rule, accompanied by increased 
intensity of polyuria. 

Pollakiuria , or abnormally frequent passing of urine, is a com¬ 
mon symptom, but stands in no distinct relation with the intensity 
of either the glycosuria or the polyuria. Sometimes there is dis¬ 
tinct pollakiuria without any polyuria, and the patient passes urine 
a dozen times a day, although the whole quantity may not exceed 
the normal. In other cases, sometimes even in severe cases, there 
is no pollakiuria, but a decided polyuria. One of my patients, who 
died in coma, used, with great regularity, to pass urine only four 
times in twenty-four hours, but each time the quantity approached 
a liter. 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


79 


Among symptoms of diabetes may be mentioned the diminution 
in the secretions and excretions other than the urine, although exact 
investigations are still scanty. Of the saliva this has been long known, 
and dryness of mouth is one of the most common complaints of dia¬ 
betics. In mild cases one often finds perspiration normal, some¬ 
times abundant, even to hyperidrosis ; but in advanced cases a 
decrease in the secretion of the glands of the skin is generally mani¬ 
fest, with asteatosis and anhidrosis and an extreme dryness of the 
skin. Gall-stones are more common among diabetics than among 
other persons, and this I consider probably the result of a decrease 
in the secretion of bile, and chiefly the water thereof.* Young 
diabetic men with undiminished sexual vigor sometimes mention 
symptoms indicative of a diminished secretion of spermatic fluid. 
The decrease in the secretions is doubtless due in part to the des¬ 
iccating influence of the hyperglycemia on the glands as well as on 
other tissues. In severe cases, however, with marasmus, atrophic 
and degenerative changes of the different glandular elements surely 
contribute largely to this result. 

Excessive hunger- —bulimia—is a common symptom in the severe 
stage of diabetes. In the mild stage it appears only in compara¬ 
tively advanced cases with a low power of assimilation and a diet 
too rich in carbohydrates, when a considerable part of the food 
passes off in the urine as glucose. 

In the severe stage the increased hunger is so far a favorable 
manifestation, as it alone enables the patient to make good the loss 
of glucose and to mitigate the consequences of the protoplasmic 
disintegration taking place in the tissues. The ingested proteids 
under such circumstances sometimes develop enormous values, and 
I have more than once seen patients who for a short time, in addi¬ 
tion to large quantities of butter and moderate portions of carbohy¬ 
drates, were able to take considerably over one kilogram of cooked 
beef a day. In far advanced cases the patient may even, with such 
food and with an excellent digestion, present a clinical picture that 


* Bouchard states that ten per cent, of all diabetics suffer from gall-stones. Even if 
this figure should be somewhat exaggerated, there can scarcely be any doubt about the 
increased frequency of gall-stones in diabetics. All other explanations than the one given 
here of the connection between diabetes and gall-stones (by I. Kraus) seem to me to 
lack any rational basis. 




8o 


DIABETES MELLITUS AND GLYCOSURIA. 


strongly resembles that presented by starvation. In both instances 
there are observed constant loss of weight, utter prostration, low 
bodily temperature, decrease in the secretions, and the presence 
in the urine of acetone, diacetic acid, / 3 -oxybutyric acid, and increased 
ammonia. The final scene increases the similarity, for death from 
starvation is partly due to the acid toxins in the blood already men¬ 
tioned, and is, so far, death from poisoning, with a clinical picture 
that strongly resembles diabetic coma. 

Instead of bulimia, anorexia is sometimes observed in cases of 
diabetes of all stages. This is a most ominous manifestation in the 
severe stage of the dystrophy, and I shall return later on to this 
subject. 

Loss of weight belongs essentially to the severe stage, but it may 
occur under varying circumstances, and it can as little as the gly¬ 
cosuria or other manifestations of derangement of metabolism be 
rightly considered clinically without reference to the food. 

During periods of great restriction or even exclusion of carbohy¬ 
drates every one, whether diabetic or not, is likely to lose in weight, 
because it is generally difficult without carbohydrates to supply the 
organism with the necessary amount of heat-units. Loss of flesh 
of this purely “ alimentary ” kind is of no clinical importance at all, 
and does not constitute a contraindication against a rational, periodic, 
rigid restriction of carbohydrates. The patient will afterward, under 
a somewhat freer diet, easily recover his loss. 

Then we sometimes find loss of weight, even in the mild stage, 
before the patient has been put upon a restricted diet, and before his 
dystrophy has been discovered. Such a loss of flesh is of greater 
importance, and generally takes place when the power of assimi¬ 
lating carbohydrates is considerably impaired and they constitute a 
large part of the food. Still, it is usually no very difficult task in 
the milder stage to check the loss of weight, or even to make it 
good, by increasing the proteids and fat of the food (and duly 
reducing the carbohydrates). 

Finally, the most marked and the most important loss of weight 
takes place in the severe stage. When the patient’s power of 
assimilating carbohydrates has reached a very low point; when he 
loses in the form of glucose even a considerable part of the ingested 
proteids; when the toxic protoplasmic disintegration of tissues 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 8 1 

entails a greater nitrogenous expenditure than income, and a daily 
deficit under any dietetic conditions ; when the tissues are still 
insufficiently supplied, although the digestive apparatus has been 
satiated, then appears the terrible diabetic autophagia. The loss of 
weight under these circumstances is, in spite of all dietetic measures, 
often exceedingly rapid, and affects not only the fat and the carbo¬ 
hydrates of the organism, but also the proteids, and probably often 
the bones, and a fatal issue may be looked for in the immediate 
future. 

The great vulnerability and diminished recuperative pozver of the 
diabetic have been long known. They are due to the hypergly¬ 
cemia and the toxins in the blood and to the dryness of the tissues, 
probably also to defective nervous influences. The changes in the 
vessels, especially the diabetic endarteritis in the smaller vessels, 
must also have a marked influence in this direction. This weak¬ 
ness is found not only in the severe stage, but it is often quite 
extreme in patients who, with restricted diet, are free from glyco¬ 
suria, but who have suffered from diabetes during many years. In 
such persons wounds remain open for a long time, heal less often 
without suppuration, and have pigmented cicatrices. The impaired 
healing power in cases of diabetes has restrained surgeons from 
many a necessary operation, and does so sometimes even yet, 
although the diabetic patient has profited still more than others by 
aseptic and antiseptic prophylaxis. Inflammatory and suppurative 
processes, especially in inveterate cases of diabetes, are much to be 
dreaded, and a carbuncle is a far more serious matter in a diabetic 
than in a nondiabetic person. 

The dry tissues, the hyperglycemia, the toxins, the defective ner¬ 
vous influences, the arteriosclerosis, and the peculiar changes in 
the small vessels of the diabetic render him more susceptible to 
gangrene than others. 

Diabetic gangrene* which sometimes develops in the sequence of 
traumatism or other accidental agency, and sometimes appears spon¬ 
taneously, is comparable to senile gangrene ; in fact, it is usually the 


* Marechal de Calvi and Hodgkin (1864) were the first to point out a causal connec¬ 
tion between diabetes and gangrene. Peyrot (1878), Giron (1881), W. Hunt (1888), 
Heidenhain (1891), N. S. Davis (1898), and others, have since treated of the subject. 




82 


DIABETES MELLITUS AND GLYCOSURIA. 


expression of both diabetes and senility. Of 38 cases of diabetic 
gangrene in the city of Philadelphia, the age in 1 case was between 
thirty and forty; in 2 cases, between forty and fifty; in 11 
cases, between fifty and sixty; in 12 cases, between sixty and 
seventy ; in 10 cases, between seventy and eighty ; and in 2 cases, 
between eighty and ninety years (Hunt). It is thus seen that the 
cases are rare before fifty, begin to be more frequent with advancing 
years, and are relatively more frequent late in life. Diabetic gan¬ 
grene is almost always of the moist variety, and is generally with¬ 
out a sharp line of demarcation. It usually attacks the lower ex¬ 
tremities, especially the feet, but it may occur almost anywhere— 
on the body, in the lungs, on the arms, the nose, the penis, etc. 
Sometimes the gangrene develops in several places simultaneously 
in smaller or larger patches. Settenbom has recently described a 
case presenting such patches with a circumference of from 10 to 15 
cm., distributed over the whole body except the head. Kaposi 
mentions a case with “ gangrena bullosa serpiginosa ” ; and Pitres, 
Rosenblath, Blau, and others have also described cases with multi¬ 
ple gangrene of the skin. Diabetic gangrene, chiefly a manifesta¬ 
tion of old age, does not usually occur in the severe stage, which is 
rare late in life and of comparatively short duration, but in cases in 
which the exclusion of carbohydrates leads to disappearance of the 
glycosuria, though many years of diabetes have had time, in 
combination with senility, to bring about the changes already 
mentioned. I have myself seen several cases in which the power 
of assimilation was comparatively quite considerable, although the 
dystrophy had existed for between fifteen and eighteen years. In 
one of the cases there was marked arteriosclerosis and atrophy of 
the kidneys. 

The prognosis of diabetic gangrene is always dubious, but even 
pulmonary gangrene is not necessarily fatal. One of my patients 
has successfully passed through this complication. In the lower 
extremities gangrene may often, under rational treatment, general 
and local, result in recovery. I have seen one case in which an 
enormous scar on the calf of the left leg reminded the patient dur¬ 
ing the last three years of his life that he had undergone such a 
process. 

The variety of gangrene due to pressure, and usually designated 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


83 


decubitus (bed-sore), is more easily acquired in diabetes than in 
other conditions, and one has to be especially on his guard against 
such a complication in the course of intercurrent diseases or other 
states that are likely to cause it. 

Among complications of diabetes with gangrene, suppuration, 
and disintegration of tissues, must be mentioned the common 
furuncle and the carbuncle , and the two rare disorders, “ le mal 
perforant" and “Raynaud's disease .” 

The furuncle is exceedingly common, and is especially to be 
found in the mild stage in fat patients ; the thin, severely ill diabetic 
usually have had no furuncle. The complication is generally not a 
dangerous one. 

The carbuncle, which generally appears on the neck or on the 
back, belongs to advanced cases, is, when associated with diabetes, 
quite a formidable disorder, and manifests a marked tendency to 
spread and to give rise to general septic infection. It causes death 
in a not inconsiderable number of cases of diabetes. “ Le mal per¬ 
forant ” (Kirmisson, Gascuel) is, as is well known, generally a 
symptom of tabes dorsalis ; if it is found in other cases one must 
suspect diabetes mellitus. It is sometimes found together with 
diabetic gangrene of the ordinary form. I have seen it several 
times, and I suppose that it occurs in at least two or three percent, 
of all cases. The small, sharp-edged, perfectly round, torpid ulcers 
may occur on one or both sides, generally on the hands or feet, and 
mostly over a joint. The innocent-looking ulcer then advances 
into the joint, and may cause extensive destruction of both the soft 
tissues and the bones and necessitate amputation. It sometimes 
leads to death. The cases of “mal perforant” that I have seen 
have presented typical symptoms of neuritis in the affected area, 
and neuritis has been repeatedly found postmortem. 

That most interesting of all forms of gangrene, Raynaud's disease , 
is rare both in association with and independently of diabetes ; but 
the considerable number of cases of diabetes thus complicated leave 
no doubt that diabetes is a predisposing cause. “ Raynaud’s dis¬ 
ease” is a vasomotor disorder, and neuritis has several times been 
demonstrated postmortem. As is well known, the disease often 
attacks peripheral parts symmetrically, as the feet, the hands, or 
the ears. It begins with strong vasomotor spasm, giving rise to 


84 DIABETES MELLITUS AND GLYCOSURIA. 

ischemia, pallor, coldness, and some loss of sensibility in the affected 
region. I presume it is this “ local syncope” that under some con¬ 
ditions may lead to scleroderma. After some time, however,—hours 
or days or weeks,—dilatation of the vessels usually follows, with 
hyperemia, cyanosis, and excruciating pains,—whether from active 
vasodilator influence or from vasoconstrictor paralysis, has not yet 
been agreed upon. We have then the “ local asphyxia,” which 
some consider identical with erythromelalgia as described by Weir 
Mitchell. After this, gangrene may set in. 

Lymphangitis and erysipelatous and phlegmonous processes threaten 
the diabetic much more frequently than healthy persons, probably 
on account of the better conditions for vegetation that he presents 
to microorganisms. Senator and Rovere have described cases of 
suppurative polymyositis with multiple abscesses in the muscles. I 
am unable to understand in what respect such a process differs 
essentially from some cases of pyemia. 

The cavity of the mouth often presents characteristic changes, 
which are of serious import to the patient and of practical signifi¬ 
cance to the physician, because they stand in a certain relation to 
the duration and the intensity of the glycosuric dystrophy. The 
breath gives at once important information, its strong odor of acetone , 
which is much like that of chloroform, denoting the severe stage 
of the dystrophy. This odor may diffuse itself throughout the 
patient’s room, often suggesting the diagnosis immediately, and 
sometimes revealing to a physician the state and the impending 
fate of some stranger passing on the street. One may sometimes 
perceive a slight uncertain odor of acetone from the mouth of a 
person in the mild stage of diabetes, as one always does from the 
mouth of anybody in a state of severe inanition and sometimes 
does from the mouths of quite healthy children. If there is no 
odor of acetone from the mouth of a diabetic patient, he is pretty 
certain to be in the mild stage. Inspection of the mouth also very 
often affords valuable information. The tongue is often somewhat 
dry in mild cases of diabetes, but otherwise it is usually little 
changed. In severe or advanced cases it is dry and marked off 
into rectangular areas by deep furrows, like the hide of an alligator ; 
the base is often covered by a brown, sometimes almost black, coat¬ 
ing, while the apex is abnormally red, with hyperemic papillae. 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 85 

Here and there one sometimes finds glossy, fleshy looking patches, 
where the mucous membrane has undergone atrophic changes. 
The teeth also undergo changes after true diabetes has existed for 
any great length of time. If I find a complete and normal set of 
teeth, I know at once that the glycosuria (and hyperglycemia) is 
either of recent date or does not amount to a true diabetes. In 
diabetics, even in the mild stage, the teeth are, as a rule, carious ; a 
smaller or greater number of them, besides, have fallen out. In¬ 
spection of the gums often leads to discovery of the causes of loss 
of teeth. A distinct gingivitis is often present, exhibiting tender, 
swollen, red areas. Here and there a drop of pus may be made to 
appear on pressure ; the bistoury may empty a little pocket of pus ; 
and the probe may, through a fistula, reach bone. These features 
belong to the common condition of alveolar pyorrhea. Sometimes 
the patient presents the ordinary symptoms arising from a more or 
less pronounced periostitis , or a pericementitis , as, I believe, the 
dentists call the process when it affects the periosteum surrounding 
the roots of the teeth. In some cases, even independently of 
senility, teeth are missing without any evidence of an inflammatory 
process and without the patient ever having suffered from symp¬ 
toms of that condition. This is in great probability the result of 
retrogression and atrophic changes in the periosteum and in the 
maxillary bones. The latter process leads to osteoporosis , which, 
there is good reason to believe, occurs in severe marantic cases 
of diabetes (see below), and which is known to occur in other 
disorders of the central nervous system ( e . g., progressive par¬ 
alysis). 

Diabetes mellitus does not per se cause any elevation of tempera¬ 
ture. Whenever fever takes place we have to do with some com¬ 
plication and must make a careful investigation for it, especially in 
the lungs. In mild cases without complications the temperature is 
normal. In severe marantic cases the temperature is below the 
normal; but, apart from coma, it is rarely below 36° C. (96.8° F.). 
In the presence of coma it sometimes sinks several hours, or even 
several days, before death to between 25 0 and 30° C. ( 77 ° an d 
86° F.). 


86 


DIABETES MELLITUS AND GLYCOSURIA. 


The Nervous System. 

The diabetic patient is, as I have mentioned, often a member of 
a nervous or even of a neurotic family in which, according to the 
two laws of heredity and transmutation, may be found most of the 
diseases that thrive on neurotic soil. We may thus find in different 
generations of the same family slight mental disturbances, developed 
psychoses, diseases of the brain and spinal cord alternating with ex¬ 
ophthalmic goiter, diabetes, gout, and other morbid processes, whose 
dependence upon the nervous system, though not perfectly estab¬ 
lished, is yet beyond doubt. 

Then it has been ascertained that certain lesions of the nervous 
system directly cause diabetes, the symptoms of which develop 
simultaneously with the nervous symptoms. 

Finally, it has been learned in the last few decades that diabetes 
per se may cause changes in the nervous elements, partly directly, 
partly through some of its complications, and especially through its 
influence on the vessels of the brain and consequent hemorrhage, as 
well as other circulatory disturbances. 

Thus, nervous disorders—central and peripheral, acute and 
chronic—are exceedingly common in conjunction with diabetes. 
Among these disorders, however, neither the severe neuroses nor 
the systematic diseases of the brain and spinal cord are at all fre¬ 
quent. Jacoby, of New York, observed three cases of epilepsy 
complicated by diabetes mellitus, and admits the possibility of a 
connection between the epileptic attacks and the diabetic toxins in 
the blood. Finlayson, Ebstein, and others also mention such cases ; 
but among nearly 200 diabetics seen in the course of the last few 
years I have not encountered one complicated by epilepsy.* Tabes 
dorsalis and diabetes mellitus have been observed in the same per¬ 
son in a number of instances ; but these and other cases of diabetes 
occurring in conjunction with organic, systematic, central nervous 
diseases constitute but a small proportion among the large number 
of diabetics, even if such complications are found somewhat more 
frequently in association with than independently of the glycosuric 
dystrophy. 


* In a male child and in some few cases in women I have seen general convulsions, 
with complete preservation of consciousness; these I considered to be hysteric. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 87 

A far less rare, but still not very common, expression of the 
neurotic tendency and of a depraved state of nutrition is a more or 
less well developed psychoneurosis. In Europeans and their de¬ 
scendants * this generally goes no further than hypochondriasis. 
Sometimes, however, the patient presents a somewhat more pro¬ 
found mental change, and the clinical picture of simple melancholia 
appears. We then generally find only the mild, active form of the 
disease, with only moderate impairment of intellectual activity, 
though a certain degree of lack of energy is found in these as in all 
cases of melancholia. Pronounced apathy, hebetude, or even 
stupor is exceedingly rare, and the same may be said of hallucina¬ 
tions. The false ideas are rarely without some real objective cause, 
and generally only represent the hypochondriacal state already 
mentioned. Sometimes, however, one finds entirely unfounded 
fixed ideas, such as are observed in developed melancholia— e. g., 
a delusion of poverty in the face of excellent material circumstances, 
etc. I have also seen instances of fully developed melancholy 
raptus with strong terror and violent tendencies. Suicide is rare, 
even among diabetics, although somewhat more frequent than 
among other persons. 

The nervous centers that preside over the metabolism of carbohydrates are 
not the same as those that perform the highest mental functions, and the con¬ 
nection between diabetes and the disturbances of these functions is most vague. 
Mild diabetes may be complicated by a true psychosis, and severe diabetes 
may leave the mental state almost intact. On the other hand, an influence on 
the mind by the diathesis can not be denied, and in diabetics of a psychopathic 
constitution hyperglycemia may contribute to the development of mental dis¬ 
ease. An analogous influence is exerted by gout (Berthier, Raynor, Savage, 
Chrichton-Browne). In a mild but fully developed case of melancholia I dis¬ 
covered also mild diabetes, with 1.3 per cent, of glucose in the twenty-four 
hours’ urine under ordinary diet. A moderate restriction of the carbohydrates 
stopped the glycosuria and was followed by immediate improvement in the 
mental state, obvious to the patient’s family. In another case of melancholia 
associated with diabetes restriction of the carbohydrates, with diminished 
hyperglycemia, did not seem to influence the melancholia at all, the patient 

eventually committing suicide. 

* 

Other pure neuroses than hypochondriasis and melancholia are 


*In the East Indian medical literature we find statements from which we may con¬ 
clude that severe mental diseases are more frequent among diabetic Hindoos than among 
diabetic Europeans. 



88 


DIABETES MELLITUS AND GLYCOSURIA. 


rare in association with diabetes. Hysteria—if properly distin¬ 
guished from purely neurasthenic neuroses—is sometimes, but not 
often, found in cases of diabetes (Gumpertz, Toralbi, Kleen, and 

Neurasthenic symptoms , both cerebral and spinal, are exceedingly 
common in diabetics, and it is rare to find such a patient entirely 
free from them. The diabetic is almost always a wretched sleeper, 
even if polyuria does not disturb him. During the day he suffers 
from another neurasthenic symptom—namely, drowsiness, which 
prevents intellectual activity without inducing sleep.* The slight 
neurasthenic headache, almost continuous, sometimes only felt as a 
sense of “ emptiness ” or of pressure, is frequent. The capacity 
for assiduous intellectual work is almost always diminished and 
memory is often distinctly impaired. Irritability is increased, as 
any physician having much to do with diabetes has learned at his 
own expense. In cases on the psychoneurotic border-line this may 
amount to a true “ iracundia morbosa,” with an unbearable temper 
and impulsive, violent acts. Spontaneous vertigo is not common, 
but vertigo at heights is present in about two-thirds of all cases 
with diminished power of assimilating carbohydrates. I have also, 
though rarely, observed agoraphobia. A host of less important 
neurasthenic sensory disturbances, in the form of hyperesthesia, 
paresthesia, and vague pains, annoy the diabetic patient. Feelings 
of cold or of heat, of the hair standing on end or being absent, of a 
more or less distinct “casque neurasthenique,” of pressure, of creep¬ 
ing, of “ plaque sacree ” or other rhachialgic manifestations, of 
shooting-pains in the limbs, etc., add to the patient’s distress. 
Pains in the epigastrium are not uncommon in diabetes, and have 
been compared to the “ crises gastriques ” of tabes dorsalis, but 
they seem hardly to be distinguishable from analogous complaints 
often made by neurasthenic patients that are not diabetic. 

Among neuralgias in diabetes, sciatica is the most common. 
Next in frequency come neuralgias of the fifth pair of nerves 
(trigeminus), especially of the inferior maxillary division. Supra¬ 
orbital neuralgia, as in other conditions, is sometimes accompanied 



* An American neurasthenic (nondiabetic) lady aptly described this condition by say¬ 
ing : “I suffer from insomnia all night and from somnia all day.” 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 


89 


by the vasomotor disturbances that constitute migraine.* All of 
these neuralgias, while generally not very intense, are quite obsti¬ 
nate, and are often bilateral. 

In 1887 1 treated at Carlsbad a case of one of those curious forms of aber¬ 
rant vasomotor neurosis that are called equivalents of migraine. The patient, 
fifty-three years old, was the principal of a school. His father, an uncle, and 
at least one cousin had suffered from diabetes. The patient himself had suf¬ 
fered from the glycosuric dystrophy for at least fifteen, probably for nineteen, 
years, and he had reached the boundary between the mild and the severe 
stage. He had not had syphilis, presented no distinct rigidity of the arteries, 
and no other ocular disorder than moderate myopia. From time to time he 
felt a sense of rigidity in the left side of the face, and at the same time paresis 
in the left arm. I saw the man during one of these attacks, which had begun 
at 2 p . m . He presented marked paresis of the left facial nerve and of the 
whole left arm ; at 5 p. m . his condition again was perfectly normal. Some 
months afterward the patient suddenly suffered a cerebral hemorrhage and in 
one of these attacks died “ apoplectico modo.” I presume that vasomotor 
neurosis in a case of long-standing diabetes, with brittleness in the vessels 
from diabetic endarteritis, is rather likely to end this way. 

Sometimes there occur functional disturbances of the secretory nerves, and 
instead of the customary decrease of secretion there may be an abundance, as 
manifested by local sialorrhea, hyperidrosis, etc. 

The muscular neurasthenia—not to be confused with the func¬ 
tional disturbances resulting from marantic and other changes in 
the muscles in the severe cases — is often marked, and even 
in a mild case the patient has often much less muscular en¬ 
durance than his general robust appearance would seem to indi¬ 
cate. Among other muscular neurasthenic symptoms there have 
also been observed, generally at night, cramp in the calves of the 
legs, which sometimes, however, is not merely functional, but a 
symptom of beginning inflammation of the posterior tibial nerve. 
The fine, fibrillary, clonic spasm is not uncommon, especially in 
the orbicularis. 

Sexual pote7icy is generally weakened, but the degree of failure 
varies greatly and has no fixed relation to the intensity of the dia¬ 
betes. This symptom often is but little influenced by hypergly¬ 
cemia, and is often found, together with other neurasthenic dis¬ 
turbances, in mild cases, as in cases of simple glycosuria or of 


* That terrible cousin of the comparatively innocent migraine—epilepsy—is, in spite 
of their angioneurotic tendencies, rare among diabetics. 

7 




90 


DIABETES MELLITUS AND GLYCOSURIA. 


neurasthenia without glycosuria. In some cases, on the other hand, 
the patient is conscious of a decided improvement after restric¬ 
tion of carbohydrates and the disappearance of glycosuria. In mild 
cases of diabetes the potency sometimes remains normal or nearly 
normal for many years ; in a small number of cases apparently trust¬ 
worthy patients make statements of virile power that painfully strain 
credulity. Sterility in diabetes will be considered later. 

Diabetic Jieiiritis and polyneuritis * are often detected, but still 
more often exist and escape detection. They certainly do not de¬ 
pend exclusively on the acetone and the acid toxins in the blood,— 
the “ acidosis,” as Naunyn terms the condition,—as they are much 
more common in mild cases (without acidosis) of long standing than 
among cases in the severe stage (with acidosis), which generally are 
severe from an early period of their existence and rarely last many 
years. In fact, the one feature common to all cases of diabetes with 
neuritis I have found to be the long duration of the dystrophy. If 
an accessory influence is present, one may find distinct neuritis in 
cases with an only slightly impaired power of assimilating carbohy¬ 
drates. The most frequent of these accessory influences are gout 
and alcoholism. Even in cases of purely diabetic neuritis (without 
gout or alcohol) the symptoms are closely similar to those of gouty 
neuritis. By this I mean that diabetic neuritis, though sometimes 
isolated and circumscribed and sometimes unilateral, is far more 
often multiple and bilateral ; that it involves especially the lower 
extremities, though I presume it may attack any nerve ; and, finally, 
that it is of a pronounced torpid character. Only rarely does the 
process set in with active symptoms, acute pains, and sensations of 
“tingling.” Usually its onset is so insidious that the patient is 
virtually unconscious of his sensory disturbance until it is disclosed 
by the physician’s investigation. Sometimes, however, the patient 
complains of a feeling of burning or of prickling, and hyperesthetic 
areas may be found upon the skin. One must not expect often to 
find distinct tenderness of the nerves on pressure. Diffuse muscular 
sensitiveness, like that due to rheumatic infiltration, is much more 


*Von Ziemssen was, so far as I know, the first to point out the occurrence of 
diabetic neuritis (1885). Thomas, Leyden, Althans, v. Striimpell, Buzzard, Charcot, 
Bury and Ross, and many others have since contributed to our knowledge of this 
subject. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 91 

common. Diminished sensibility to pin-prick, or the esthesimeter, 
or to a tube filled with hot water is frequently present. Complete 
analgesia and anesthesia are exceedingly rare ; I have not seen a 
single instance of either, though cases so complicated are recorded 
in literature. In rare instances I have observed retarded sensibility. 

Apart from the frequent spasm of the muscles of the calf, which 
probably is caused by neuritis only in rare cases, motor disturbances 
are much rarer than sensory. If the neuritis is intense, and there is 
also general debility and marasmus, marked reaction of degeneration 
to the electric current is sometimes present, and in rare cases pro¬ 
found functional disturbance. Foot-drop and complete paraplegia 
have been observed in some cases, and many instances of paresis or 
paralysis of single muscles or of groups of muscles are recorded 
(Charcot, Buzzard, and others). 

The neuritis often causes trophic changes within the distribution 
of the nerve or nerves affected. Among such manifestations are 
local hyperidrosis or anhidrosis; atrophic, thin, “glossy” skin; 
cutaneous eruptions, as urticaria, eczema, herpes zoster, etc. (see 
below) ; discolored, thick, brittle nails, which readily fall out, etc. 
The “ mal perforant ” and “Raynaud’s disease” are undoubtedly 
manifestations of neuritis, which probably also contribute to the 
development of other gangrenous processes, whether occurring as 
a single area of sphacelus or disseminated in patches. 

Absence or weakening of the knee-jerk (and other tendinous and 
cutaneous reflexes) is a frequent symptom of diabetes.* The ex¬ 
planation for the disappearance of the tendinous and other reflexes 
is to be sought in changes in both peripheral and central nervous 
elements (see below). Inflammation of the crural nerve has been 
found in cases with absence of knee-jerk. According to Erlen- 
meyer, the cause is generally to be found in changes in the “ ban- 
delettes externes ” of Burdach’s tracts in the posterior columns of 
the spinal cord. In other cases postmortem investigation has failed 
to disclose any nervous change whatever (Nonne, Rosenstein), and 


* Absence of the knee-jerk was noted by Marinian and by Bouchard in 1884. It 
occurs also in tabes dorsalis and sometimes in apparently normal individuals. This lat¬ 
ter occurrence seems to be much more frequent in some races than in others. Prof. H. 
C. Wood, of Philadelphia, has told me that he has found it strikingly often in South 
Americans. 




9 2 


DIABETES MELLITUS AND GLYCOSURIA. 


it seems possible that the absence of the knee-jerk may sometimes 
be the result of a purely functional disorder, i. e., a change with¬ 
out discernible anatomic basis. 

The knee-jerk is found absent in both the mild and the severe 
stage, but much more frequently in the latter than in the former. 
Apart from this fact, absence of the knee-jerk has no distinct prog¬ 
nostic significance, and it is sometimes found in cases in which 
the diabetic syndrome has remained stationary in a mild form for 
many years. Often the knee-jerk is weakened. Sometimes it re¬ 
mains distinct for a long time on one side after having disappeared 
from the other. In some few cases I have observed that one or 
both knee-jerks have reappeared after having been absent for some 
time.* 

Statistics show that the knee-jerk is absent in from 7.6 to 50 per cent, of 
all cases of diabetes. The former figure is much nearer the truth than the 
latter. Tests even of the almost exclusively severe cases seen in hospitals will 
show that the knee-jerk, at least among Anglo-Saxon or Teutonic diabetics, 
though often weakened, is still distinct in the majority of cases. As I write this, 
an analysis of 100 cases of diminished power of assimilating carbohydrates, 
taken at random from my records of private practice, shows that the knee-jerk 
was absent in 7 of 39 severe cases, in 7 of 51 cases of true though mild diabetes, 
and in 1 case of simple glycosuria of many years’ standing from among 10 
similar cases. Of the 85 cases in which the knee-jerk remained distinctly, it 
was weakened in many and in several it was absent on one side. When the 
result of the investigation was at all uncertain, the knee-jerk has always been 
recorded as absent. 

The other tendinous reflexes and the cutaneous reflexes may also 
be weakened or lost. It is important, however, to remember that 
the reflex contraction of the pupil on exposure to light is not lost 
in uncomplicated cases of diabetes, and the Argyll-Robertson pupil 
(contracting in accommodation, but not on exposure to light) points 
to a complication with central nervous diseases of organic origin. 

In causing changes not only in the peripheral nerves, but also 
in the spinal cord, especially its posterior columns, diabetes mellitus 
sometimes presents an anatomic similarity to tabes. Diabetes also 


* This may or may not be a favorable sign. We know that removal of the influence 
of higher centers is capable of heightening a reflex dependent on lower centers. In a 
case of diabetes it may happen that an absent knee-jerk reappears after acute cerebral 
disturbances of paralytic character. 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 


93 


is almost always associated with more or less pronounced neuras¬ 
thenia or a group of symptoms sometimes attended with functional 
disturbances similar to those that occur in tabes. It is, therefore, 
not astonishing to encounter cases of diabetes presenting a clinical 
picture that resembles more or less closely that of true tabes. This 
“ psendotabcs diabetica ,” like all other forms of pseudotabes, may be 
attended with more or less hyperesthesia, paralysis, or ataxia. The 
individual case, however, rarely comports with the somewhat arti¬ 
ficial division of Leyden, but presents symptoms of each kind. 
Sometimes, apart from true tabes, diabetic patients present hyper¬ 
esthetic or anesthetic areas, with peripheral neurasthenic pains, 
which, though less violent, may resemble the lancinating pains of 
tabes, and be associated with epigastric pains that may be mistaken 
for “ crises gastriques ” ; we further find absence of tendinous 
reflexes, sexual impotence, a neurasthenic, tired, gait, or—if the 
multiple neuritis is pronounced in the lower extremities—high- 
stepping, uncertain, ataxic movements of the legs in walking and 
an unsteadiness in standing with closed eyes, much like Romberg’s 
symptom, etc. In short, diabetic cases of long standing may ex¬ 
hibit sensory, motor, secretory, and trophic changes of various 
kinds, that cause difficulty in distinguishing this “pseudotabes peri- 
pherica diabetica ” from true tabes, especially from “ neurotabes 
peripherica.” The absence or the presence of tabetic ocular symp¬ 
toms, which usually appear early in true tabes, especially reflex im¬ 
mobility of the pupils, may sometimes govern the decision, while in 
other cases it may be necessary to reserve the diagnosis for a 
time. 

A combination of diabetes mellitus and true tabes is rare, but, apart from 
being merely accidental, it may be brought about by the sclerotic process of 
tabes attacking the diabetic center in the floor of the fourth ventricle of the 
brain. Under such circumstances there will (always ?), according to Guinon and 
Souques, be found: (i) anesthesia within the distribution of the trigeminus, in 
consequence of destruction of the center for that nerve, and (2) increased 
frequency of the pulse, in consequence of destruction of the center for the 
pneumogastric nerve. 

The question of a connection between tabes dorsalis and diabetes has been 
most elaborately discussed in recent years. Frerichs, in 1863, reported a case 
of tabes associated with diabetes ; Smith, in 1883, had a patient with tabes asso¬ 
ciated with glycosuria; and Oppenheim, in 1885, presented a similar case to 
the Society of Physicians of Berlin. Absence of knee-jerk, one of the earliest 


94 


DIABETES MELLITUS AND GLYCOSURIA. 


symptoms of tabes, has since 1884 been noted in many cases of diabetes, while 
from the eighties the expression “ pseudotabes ” of Leval-Piquechef became 
current, and our knowledge of the polyneuritis of diabetes and of “ pseudo- 
tabes peripherica diabetica ” on the one hand, and of “ neurotabes peripherica ” 
in true tabes on the other hand, developed. A vast literature has grown, from 
which I select especially the names of v. Ziemssen, Rosenstein, Lecorche, 
Eichhorst, Marie and Guinon, v. Hoesslin, Price, Auerbach, Buzzard, Leyden, 
Althans, Charcot, Auche, Burns, Vergely, Ross and Bury, Naunyn. 

In true tabes one rarely finds glycosuria. Eulenburg observed one such 
instance among 125 cases of tabes, and Gilles de la Tourette, 3 among 100 
cases, while Marie and Guinon found no case of glycosuria among 50 of tabes. 
These figures illustrate the superficial character of the investigations, and 
it is certain that one would find pathologic quantities of glucose in the urine in 
a much larger percentage of average individuals ; but, on the other hand, 
these figures permit us to draw the conclusion that the combination of tabes 
and diabetes mellitus is a rare one. 

I have seen a number of, in part merely neurasthenic, in part really 
neuritic, cases of “ pseudotabes,” but only one case of true tabes complicat¬ 
ing diabetes. This case occurred in a clergyman, sixty-two years of age, who 
somewhat feebly denied a history of syphilis, but who was well known in his 
younger days to have sinned much and indiscriminately against sexual morality. 
This somewhat unfaithful servant of the Church later in life, after marriage, 

.—and especially after becoming completely impotent,—turned his iniquitous 
ways from the temple of Venus to that of Bacchus, and sometimes shocked his 
flock by being terribly drunk. Still, these triumphs of the flesh, thanks to the 
careful control of his strong-minded wife, caused such rare interruptions in an 
otherwise exceedingly moderate mode of life, that an alcoholic basis for neu¬ 
ritis could be excluded. But there was distinct, though not pronounced, locomo¬ 
tor ataxia, with Romberg’s symptom, a feeling as if cotton were under the feet, 
lancinating pains in the upper part of the legs, absence of tendinous reflexes, 
Argyll-Robertson pupil, an unreliable sphincter ani, and a quick pulse. The 
urine, of normal quantity, generally contained, with a free diet, somewhat more 
than 1 per cent, of glucose. Not then having in view the publication of any 
article on diabetes, I made no more careful investigation than that indicated 
by the facts recorded. 

In advanced stages of diabetes, or, rather, in cases of long stand¬ 
ing, when diabetic endarteritis has had time to render the vessels 
brittle, accidents from intracranial hemorrhage are not uncommon. 
I believe that small hemorrhages often take place under such con¬ 
ditions without causing symptoms sufficiently pronounced to attract 
the notice of either the patient or the physician, and especially that 
a number of such hemorrhages may take place simultaneously 
with similar small ecchymoses that occur in conjunction with hem¬ 
orrhagic diabetic retinitis. In some cases the patient may com- 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


95 


plain of deep-seated pains in the head, nausea, ocular disturbance, 
etc., but the condition often remains so vague and indistinct that 
the physician is easily misled to consider it an insignificant vaso¬ 
motor disorder, until some serious accident directs attention to the 
warnings. The patient may suddenly exhibit apoplectic symptoms, 
and subsequently become monoplegic or hemiplegic, with hemian¬ 
opsia, diplopia, amblyopia, strabismus, ptosis, etc. The nervous 
symptoms included in Weber’s syndrome have several times been 
observed in cases of diabetes. The oculomotor nerve of one side is 
paralyzed, with resulting divergent strabismus, crossed diplopia, 
dilatation of the pupils, paresis of accommodation, and ptosis ; while 
on the other side the lower branch of the facial nerve, the arm, and 
the tongue are paretic or paralytic. In other cases the abducens or 
trochlear nerve is paralyzed. The paralysis of the facial nerve in 
diabetes is often central, but not rarely is it peripheral. 

There is one thing to be said about these diabetic hemorrhages 
—they indicate a more favorable prognosis than any other kind 
of cerebral hemorrhage, except, perhaps, the syphilitic ; I pre¬ 
sume because the bleeding often takes place from quite small ves¬ 
sels. Even when the hemorrhage has left the patient unconscious, 
the symptoms sometimes quickly disappear. The patient, how¬ 
ever, is in constant danger, and a new attack may bring life to an 
end. 

In some cases, when a chronic nephritis is present, intracranial 
hemorrhage may have to be diagnosticated from uremia. 

In autopsies after diabetes, whether of the mild or the severe 
stage, it often happens that both the naked-eye and microscopic 
examination fail to disclose any change in the nervous system. 
This may be so even when neither the liver nor the pancreas is 
materially altered, and when clinical observation has given reason 
to believe that the glycosuric dystrophy has, as usual, been depend¬ 
ent upon nervous disturbances. 

It is proper to point out that, on the other hand, it is not rare to 
find postmortem tumors and other changes in the brain, which 
must have affected decidedly the fourth ventricle, without glycos¬ 
uria ever having been observed during life (Verron, Lepine). 

In autopsies in other cases of diabetes there are found in the 


9 6 


DIABETES MELLITUS AND GLYCOSURIA. 


central nervous system changes that there is good reason to con¬ 
sider as either the cause or the effect of diabetes. From what has 
already been said, it is generally easy to form an idea as to which 
of the two one has to deal with, and it seems worthy of remark 
that, in order to cause glycosuria, brain-disease need not necessarily 
directly affect Bernard’s center in the floor of the fourth ventricle. 

In chapter hi it was mentioned that there have been observed in 
the brain after diabetes extravasation of blood, atheromatous pro¬ 
cesses, aneurysm, softening, sclerosis, colloid or fatty degeneration, 
new growths (fibroids, gliomata, sarcomata, osteomata), and the 
cysticercus racemosus, through which Michael’s name has become 
familiar to all students of diabetes. It was also pointed out that 
general paralysis and akromegaly have often, and multiple sclerosis, 
tabes dorsalis, paralysis agitans, meningitis, and syphilitic disease of 
the brain have sometimes, been seen in association with either simple 
glycosuria or diabetes. 

A common condition found after diabetes is dilatation of the 
smaller blood-vessels, with small hemorrhages into the brain 
(Frerichs), probably as a result of changes due to diabetes endar¬ 
teritis (see below). The small cysts mentioned by Saundby and 
others are probably the residual products of such hemorrhages. 

Dickinson, in 1870, described perivascular spaces filled with detri¬ 
tus occurring throughout the whole cerebrospinal system in cases of 
diabetes. It is a seductive theory to consider vasomotor paralysis, 
or paresis, strong dilatation of the vessels of more or less transitory 
character, and pressure with retrogressive metamorphosis of the 
surrounding central nervous elements in the floor of the fourth 
ventricle, as a cause of diabetes ; but the perivascular spaces de¬ 
scribed by Dickinson often occur independently of diabetes, and 
neither German (Frerichs) nor English (Taylor and Goodhart) 
observers are inclined to ascribe any such significance to the con¬ 
dition named. 

Glycogen, which seems, in severe causes of diabetes, to be in¬ 
creased in other organs as it is decreased in the liver, has been 
found in much greater quantity than normal in the brain after dia¬ 
betes (Futterer). 

It seems that diabetes not rarely causes certain changes in the 
spinal cord, the most common of which is sclerosis of the posterior 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


97 


columns, especially Goll’s and Burdach’s tracts, more rarely of the 
lateral columns (Williamson, Leyden, Minor, Sandmeyer, Leich- 
tentritt, Kalmus, Hensay). 

Boccardi’s studies of the spinal cords in dogs made diabetic by 
extirpation of the pancreas have yielded valuable information. The 
degeneration is not symmetric and has no systematic character. It 
was found essentially in Goll’sand Burdach’s tracts and in the zone 
external to them (Lissauer’s tracts), close to the posterior nerve- 
roots. Sometimes it encroached almost upon the whole of the 
posterior columns, so that only the posterior parts of Golfs tracts 
and a thin zone of Burdach’s tracts remained free. Changes in the 
lateral columns were much less common, and, when present, were 
found in Gowers’ tracts and in the crossed pyramidal tracts. 
Alterations in the sheath and in the axis-cylinders of the nerves,— 
the former being thinner and the latter having a lacerated appear¬ 
ance—were found even a short time after the onset of severe dia¬ 
betes. The proliferation of the areolar tissue and the process of 
sclerosis began subsequently. The gray substance also was 
changed ; degenerated, enlarged, hyaline cells being found in the 
anterior and posterior cornua and in Clark’s columns, and the nuclei 
of these cells staining with difficulty or not at all. Here and there 
were observed lacunae, like those described by Charcot and Joffroy. 
Sometimes the endarteritis with endothelial desquamation, described 
by Ferraro, was noted; according to Boccardi, it was rather the 
exception than the rule. 

Nonne observed (in vivo and postmortem) chronic anterior polio¬ 
myelitis as a complication in a case of severe pancreatic diabetes. 

Toward the close of the eighties, Price, Eichhorst, and Auche 
described diabetic neuritis, all three finding parenchymatous degen¬ 
erative neuritis with uneven, vacuolar sheath, with the axis-cylinder 
segmented or absent. It seems that these alterations are present 
most frequently in the anterior and posterior tibial nerves. Hensay 
noted similar changes in the facial and spinal accessory nerves. 
The crural nerve also has been found in this condition.* 


* The knee-jerk in this case had been absent during life. Changes in the peripheral 
nerves, however, unless sufficiently far advanced to destroy conductivity, could not alone 
cause loss of the knee-jerk. Even though our present means of investigation are in¬ 
capable of detecting changes in the cellular nervous centers, such changes may exist, and 




98 


DIABETES MELLITUS AND GLYCOSURIA. 


The pneumogastric nerve has several times been found abnormal, 
sometimes sclerotic and thickened (Percy, Fleury), sometimes com¬ 
pressed by tumors (Anger, Frerichs, Henrat, Neumann), sometimes 
atrophic from other influences than tumors (Lubinoff). Eichhorst 
found it the seat of a parenchymatous neuritis. 

The sympathetic nervous system , which has been studied care¬ 
fully, since it has been known that lesions of different parts 
thereof may give rise to glycosuria, has often been found in a 
pathologic condition. The changes have generally been found in 
the celiac ganglion, and have usually been of a sclerotic, more 
rarely of a simply atrophic, nature. 


Circulatory System. 

In inveterate cases of diabetes the heart is never very 
strong. The sounds are often weak and distant, the systolic 
elevation in the sphygmogram being often low and the pulse 
uneven, while the patient complains of the usual symptoms 
of weak heart if great demands are made on the circulatory 
apparatus. This deficiency is usually present in only a moderate 
degree, and the pronounced fatty heart is comparatively rare. 
Still, the fatal issue from this cause, by its similarity to sudden 
death in some cases of coma, has several times contributed to the 
number of false reports of death in coma apart from the severe 
stage and without “ acidosis.” 

The pulse varies exceedingly in diabetes. Its frequency, how¬ 
ever, is distinctly increased in about 75 per cent, of all cases of 
severe diabetes, and it is not rare in such cases, apart from 
complications and from diabetic coma, to find a pulse of 100 or 
more. I think this must be caused by the irritating influence of 
the toxins on the heart’s own sympathetic centers more often than 
by any paralyzing action on the center for the pneumogastric 
nerve. If one should speak of a diabetic type of pulse, it would be 
the small, feeble pulse of great frequency. 

Organic changes in the valves of the heart are generally brought 


may be expected after the operation of marantic and toxic influences of long standing. 
To such changes may be ascribed both the absence of the knee-jerk and an important 
role in the production of peripheral nervous disturbances. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 


99 


about by chronic endarteritic processes and the aortic valves are 
most commonly attacked. Changes in the mitral valves do not seem 
to me to be much more common in association with diabetes than 
independently thereof, and Lecorche’s statistics showing such 
changes in 12.3 per cent, of all cases of diabetes are to me inex¬ 
plicable. 

The most frequent macroscopic alteration in the circulatory sys¬ 
tem in diabetes consists in atheromatous processes tending to arterio¬ 
sclerosis which, excluding the juvenile cases, may be detected by 
palpation during life in about 20 per cent, of all cases. It is a 
feature essentially of inveterate cases, and is thus much more com¬ 
mon in those of long standing, though in what I persist in calling 
the mild stage, than in cases that belong to the severe stage and 
rarely persist for any considerable number of years. I should 
think that the glycemia and other blood-toxins are responsible for 
the condition ; but an influence arising from enfeebled vasomotor 
activity may possibly also contribute to the result. In the presence 
of pronounced arteriosclerosis one often finds alcoholic or syphilitic 
complications. In rare cases the atheromatous and consequent 
conditions of the arteries of the brain are not the effect but the 
cause of diabetes. 

Atrophic and degenerative conditions of the myocardium sometimes 
attend diabetes, though they are much more rarely detected during 
life than after death. 

Much has been said and written about angina pectoris compli¬ 
cating diabetes. The attacks of pain and the asthmatic disturb¬ 
ances that sometimes occur in cases of diabetes—more often during 
the night than by day, like all sensations called angina pectoris— 
are either the expression of organic disease of the heart, usually 
resulting from changes in the coronary arteries and in the myo¬ 
cardium, or they are manifestations of less important neuralgic or 
rheumatic conditions in the chest-wall, which, especially in “ner¬ 
vous ” persons, may cause great momentary suffering. Both the 
c ^first kind, the true, dangerous, “organic” form of angina pectoris, 
_jand the latter kind, the comparatively insignificant, “nervous” 
form of pseudo angina pectoris, are more common among diabetics 
than among other individuals. In most cases of diabetes present¬ 
ing such disturbances that I have seen, the attacks recurring at 


100 


DIABETES MELLITUS AND GLYCOSURIA. 


long intervals for years, the failure to detect symptoms of organic 
disease on careful physical examination, the presence of rheumatic 
infiltrations or of neuralgic symptoms in the chest-walls, the differ¬ 
ence in the radiation of the pains from what usually takes place 
in true angina, and the manifest influence of purely rheumatic and 
nervous causes, have led me to attribute the symptoms to the 
“ nervous ” form, pseudo angina, which seems to me decidedly 
more common than the true angina. 

Among the rarer complications of diabetes there occur sometimes, 
though only in advanced cases, numbers of petechise, due to small 
subcutaneous hemorrhages , most frequently on the lower extremities, 
and probably dependent on brittleness of the small vessels caused by 
the diabetic endarteritis described by Ferraro. 

The heart , in autopsies of cases in which there has been pro¬ 
nounced marasmus, often appears in a state of brown atrophy. In 
other cases the organ shows no distinct alteration. In at least 15 
per cent, of all cases some enlargement, which usually affects the 
whole organ, is manifest. Pronounced fatty degeneration is rare. 
Atheromatous changes in varying degree are common, but other 
endocarditis or valvular alterations are not. 

Dr. Jaques Mayer found, clinically, enlargement of the heart in 21.6 per 
cent, of cases of diabetes in a first series; and in a later series 27 per cent. 
The latter figure is nearly twice as high as the 15 per cent, at which I arrived 
in the same manner—a difference that, as I have found after consultations 
with my esteemed colleague, depends upon differences in opinion concerning 
the physical basis for the diagnosis. Dr. Mayer himself, in an investigation of 
the postmortem records of the city of Berlin, did not obtain a higher figure 
than 13 per cent. He mentions the chemic irritation of the increased amount 
of sugar and urea in the blood as a cause ? of the hypertrophy without further 
explanation. O. Israel has shown experimentally that in extreme cases the 
kidneys become unable to fulfil their function of eliminating urea and that the 
heart attempts to make good this deficiency by hypertrophy of its left ventricle 
(injections of sodium nitrate and of urea in horses and dogs). For my part, I 
am inclined to ascribe the rather large percentage of cases in which hyper¬ 
trophy of the heart attends diabetes to (1) the adiposity which is common in 
diabetes, and which often per se causes enlargement of the heart; (2) the 
atheromatous changes in the vessels and the obliterating and desquamative 
endarteritis of the small vessels (Lecorche, Ferraro); (3) the polydipsia and 
the increased quantity of water passing through the system. The last two 
influences must increase the burden of the heart and tend to produce a work- 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


IOI 


ing hypertrophy. In some cases there coexist the causes of hypertrophy 
resulting from cirrhosis of the kidney, which, according to the prevailing views 
of trustworthy investigators, consist in more than the narrowing of the blood- 
current. An irritating action of the blood-toxins on the vasoconstrictors might 
especially be thought of. The mesenteric vessels, however, which exert so 
important an influence on the arterial pressure, are in diabetic patients prob¬ 
ably much oftener dilated than constricted. 

Diabetic endarteritis of the small vessels (Ferraro, Strauss, Boc- 
cardi) seems to be very common and may exert an important influ¬ 
ence in the causation of hemorrhages and of degenerative pro¬ 
cesses in the tissues. It generally causes desquamation of the 
endothelium (Ferarro), and sometimes obliteration of the vascular 
lumen (Lecorche). The brittleness of the small vessels in cases of 
inveterate diabetes is manifest, and finds expression in the extrava¬ 
sations into the brain, the retina, and the cutaneous and other 
tissues.* 

Diabetic blood presents distinct changes of a physical anatomic 
and chemic nature. To the last I shall return later. The per¬ 
centage of water has been found both increased and diminished. 
Von Jaksch found it diminished in every one of io cases, in which it 
ranked from 66.46 per cent, upward, but never reached the normal, 
72.28 percent. The specific gravity was found by Hammerschlag 
to be increased to 1.064; by Davy, to be 1.061 ; by Nasse, to be 
diminished to 1.048. The number of red blood-corpuscles is 
usually high (A. James and others), except in bronze-colored dia¬ 
betes (see below), in which the number is much diminished, and 
marked hemosiderosis, due to the products of disintegrated red 
blood-corpuscles, is found in almost all of the organs. Bremer, 
Williamson, and others have found that the red corpuscles in dia¬ 
betic blood are stained in a different way by methylene-blue and 
other dyes than those in normal blood (see below). Habershon 
found marked leukocytosis in diabetic blood, the number of white 


* Rosenblath, as early as 1888, saw the walls of the small vessels thickened in an 
advanced case of diabetes. The case is surrounded with some interest on account of 
the presence of numerous small hemorrhages or ecchymoses strewn over the skin of the 
legs. Above the ecchymoses the skin in many places presented necrotic areas, which 
invaded the papillary body and about half the depth of the entire cutis. T he lungs con¬ 
tained circumscribed gangrenous areas, and the tongue and the esophagus were the seat 
of numerous ulcers. 



102 


DIABETES MELLITUS AND GLYCOSURIA. 


blood-corpuscles diminishing with restriction of carbohydrates and 
increasing during coma. Bettman, in a case of diabetes compli¬ 
cated by exophthalmic goiter, observed the number of white blood- 
corpuscles undergo diminution with a free supply of carbohydrates. 
Neusser found around the nuclei of the leukocytes in diabetic 
blood small particles that stained black with a modification of Ehr¬ 
lich’s solution (“perinuclear basophilia”). 

It has been known since the end of the eighteenth century that 
the blood of diabetics sometimes exhibits a peculiar whitish color, 
owing to the numerous particles of fat present ,—diabetic lipenna ,— 
which may reach 11 or 12 per cent. (Lecanu, D. Gerhardt, after 
Naunyn). After a rich meal the percentage of fat in the blood 
may reach high figures in healthy persons ; but the lipemia in 
diabetics, like that which attends some other pathologic conditions, 
may occur on an empty stomach (Naunyn). The intimate causes 
of the condition are unknown.* 


Respiratory Organs. 

The most common pulmonary complication of severe diabetes 
mellitus is tuberculosis. While this pulmonary disease ordinarily 
causes the sacrifice of from one-seventh to one-fifth of mankind, it 
attacks, according to Griesinger, 72 per cent, of diabetics in the 
severe stage and destroys 39 per cent. These figures apply only 
to severe cases, and are never reached outside of hospitals. 

In private practice, especially in watering-places such as Carlsbad, 
the proportion of patients with tuberculosis of the lungs is a low 
one and the patients are usually in a light stage and in fairly good 
nutritive state. This observation would seem to show that hyper¬ 
glycemia predisposes less to pulmonary tuberculosis than does 
marasmus. It is often said that tuberculosis of the lungs is much 
more quickly fatal when associated with, than when independent of, 
diabetes; but any practitioner with a large number of diabetic 
patients knows that the difference in this respect between diabetic 
and nondiabetic patients with the same degree of marasmus is but 


* Our knowledge of changes of the blood in different diseases is only developing, and 
some of these observed in diabetic blood apparently do not belong exclusively to 
diabetes. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. IO3 

slight. The results in cases of pulmonary tuberculosis complicating 
diabetes is not rarely that usual with the condition first named ; 
but in many of these cases, however, the termination is that com¬ 
mon with severe diabetes, namely, diabetic coma. 

Diabetes mellitus seems to some extent to predispose to acute 
croupous and lobular pneumonia, which, by reason of the tendency 
to severe complications, the weak heart, and the generally low con¬ 
dition, makes the prognosis worse than it would otherwise be. 
Still, one ought not to despair of a favorable issue, and I have had 
several diabetic patients that have passed through acute pneumonia 
—in one both lungs being attacked. When acute pneumonia occurs, 
the glycosuria is generally diminished in a marked degree ; in rare 
cases the reverse effect has been observed (Naunyn). 

Inflammatory processes in the lungs in diabetic patients, espe¬ 
cially in inveterate or advanced cases, are much more likely to 
induce gangrene than in nondiabetics. In Naunyn’s work, pub¬ 
lished after the Swedish edition of this book had appeared, the 
great German clinician distinguishes between two forms of pul¬ 
monary gangrene : the acute and the chronic. I have seen only 
instances of the first, but Naunyn considers one about as frequent 
as the other. 

The acute form generally begins as a croupous pneumonia, and 
is often attended with hemoptysis and abundant bloody and puru¬ 
lent sputa, which generally lack the customary odor of gangrene. 
This disorder lasts at the longest for a few weeks. After death 
one finds in the lungs gangrenous and purulent cavities, which 
usually contain bacilli or other fungi (Zenker, Furbringer), but 
which often are not very offensive to the sense of smell. One of 
my diabetic patients, who is still alive, recovered some years ago 
from this complication. Marklen has observed a similar case. A 
fatal issue is naturally the more common termination. 

The other chronic form of pulmonary gangrene complicating 
diabetes begins as a catarrhal condition, with fever and bloody or 
purulent, often offensive, sputa, and may last for years, until hemop¬ 
tysis or marasmus brings about a fatal issue. Naunyn observed 
this complication only in elderly patients. 


104 DIABETES MELLITUS AND GLYCOSURIA. 

Digestive Organs. 

I have already mentioned the diabetic changes that take place in 
the cavity of the mouth. I would here refer only to the important 
circumstance that in the diabetic the power of mastication is likely 
to be much impaired , on account of caries or loss of the teeth. 

The saliva is often distinctly diminished, and dryness of the 
mouth is a common complaint. Besides, the saliva, particularly in 
certain cases, is often acid ; but, apart from the predisposing influ¬ 
ence this may have with regard to caries, it is rather of theoretic 
than practical interest. 

The gastro-intestinal tract in diabetic patients generally fulfils its 
functions quite well so far as digestion and absorption are concerned, 
and advanced changes are exceptional. 

A most remarkable circumstance is the rarity of distinct dilata¬ 
tion of the stomach. One certainly finds often, clinically and post¬ 
mortem, that the limits of the stomach are rather extended, but not 
beyond what may be considered normal; and clinically pronounced 
dilatation certainly does not occur in one per cent, of all cases of 
diabetes. 

The diminution in all of the secretions (except the urine), which 
there is reason to believe occurs in diabetes, is not sufficient to 
impair digestion, and may, in many cases, be made good in the 
stomach and the remainder of the digestive tract by a hypertrophy of 
the secretory glands (see below). When I began to make analyses 
of the gastric juice, I made examinations in a considerable number 
of cases of diabetes, but only rarely found anomalies of composi¬ 
tion or of digestive power. This experience is in accord with the 
results obtained by Honigmann, Rosenstein, Gans, and others. 
Numerous and exact investigations into the absorption of various 
foods, as well as careful fecal analyses, also have demonstrated that 
absorption from the gastro-intestinal tract is, as a rule, normal or 
nearly normal.* 

Slight dyspeptic and catarrhal troubles are, of course, quite 
common among diabetics as among other persons. During periods 
in which the use of bread and vegetables is interdicted or rigidly 
restricted, manifest gastro-intestinal catarrh, with diarrhea and 


*See Weintraud’s masterly treatise in “ Bibliotheca medica,” i, Cassel, 1893. 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 105 

sometimes with fetid stools, is especially prone to occur, and not 
rarely necessitates a greater allowance of carbohydrates. 

Then there is a small class of diabetic patients who exhibit a 
digestive deficiency of a grave nature. These cases generally belong 
to the severe, or at least to a very advanced, stage of diabetes, and 
depend upon primary or secondary degenerative processes in the 
pancreas or in other glandular elements of the digestive apparatus. 

Hirschfeld * has published seven such cases from his own and from 
Frerichs’ and Kulz’s experience. In these, from 29.4 to 47.2 per 
cent, of the ingested fat and from 30 to 45 per cent, of the ingested 
proteids were found in the feces. Even in these cases the car¬ 
bohydrates were fairly well digested and absorbed. This certainly 
does not occur when the pancreas is in an advanced abnormal con¬ 
dition, and Abelmann found in the feces of Minkowski’s dogs, after 
extirpation of the pancreas, almost the whole quantity of ingested 
carbohydrates, upward of 43 per cent, of the emulsified and nearly 
the whole of nonemulsified fat, and as much as 56 per cent, of the 
proteids. As a rule, the fat is the kind of food that most fre¬ 
quently and to the greatest extent remains undigested and unab¬ 
sorbed, even independently of the great variations that occur in 
each individual case (Sandmeyer). 

The deficient absorption of fat, which is apparent without closer investiga¬ 
tion from the light color of the feces, has long been observed in diabetes, 
and has been ascribed to disease of the pancreas. Bright, Eliotson, Frerichs, 
Fles, and Silver observed fatty stools in diabetes, but their patients also suf¬ 
fered from retention of bile and icterus. Le Nobel noticed similar stools in 
diabetes without biliary retention. Claude Bernard, by experiment, came to 
the conclusion that the pancreatic juice is necessary for the absorption of fat. 
Senn observed fatty stools after extirpation of the pancreas. William T. Bull 
and Hartsen mark a like observation in patients with pancreatic cysts, and the 
latter found the extract with ether from pigeons’ stools three times the normal 
after extirpation of the pancreas. Von Mering, Minkowski, and Abelmann, 


* See Hirschfeld’s interesting paper in “ Zeitschrift f. klin. Med.,” Berlin, 1891. It 
is difficult to understand why these cases should be described as ‘ ‘ eine neue klinische 
Form von Diabetes.” The absence of polyuria is not rare in diabetes, and in most 
of the seven cases the polyuria, according to Hirschfeld’s own figures, was manifest. 
The cases present no peculiarity beyond the deficient digestion, and the establishment of 
artificial clinical forms is undesirable. In one of the cases, which ended fatally from 
marasmus, the glycosuria ceased with a strict diet. The pancreas was either carcino¬ 
matous or atrophic or not distinctly changed. 

8 



io6 


DIABETES MELLITUS AND GLYCOSURIA. 


finally, have observed analogous conditions after extirpation of the pancreas in 
dogs. Thus, it is finally established that pancreatic juice plays an important 
role in the absorption of fat. It is also known that the pancreas is in some 
way necessary to prevent hyperglycemia, and that the destruction of this organ 
is followed by glycosuria. It has, however, not been shown that every diabetic 
patient who, apart from retention of bile, does not digest fat suffers also from 
disease of the pancreas ; while, on the other hand, it is positively known that 
this organ may be greatly changed without noteworthy impairment in the ab¬ 
sorption of fat (Hartsen, Fr. Muller) and without diabetes resulting (Minkowski). 
It is known, further, that there are sometimes in cases of diabetes reasons un¬ 
connected with the pancreas for digestive deficiency. 

Habitual constipation is, in consequence of marasmus, and an 
atonic state of the bowels, deficient innervation, etc., still more 
common among diabetics than among other individuals, and any 
tendency in that direction is likely to become manifest with rigid 
restriction of carbohydrates. 

In connection with a consideration of the digestive apparatus in 
diabetics illustrations are not wanting of the great frequency of 
purely nervous symptoms in association with the diabetic syn¬ 
drome. Gastro-intestinal neuroses are exceedingly common among 
diabetic patients. It would carry me far beyond my purpose—as 
it would be beyond my power—to describe here all of the different 
neuroses of this kind that may occur in diabetes. The most fre¬ 
quent of these belong to that group of which a part generally is 
called nervous dyspepsia or gastric neurasthenia, but which, on 
account of its manifold sensory and motor disturbances, referred to 
different parts of the digestive tract, I prefer to designate gastro¬ 
intestinal neurasthenia. The patient often suffers from inexplicable 
variations in appetite,—which may one day be excellent and the 
next fail entirely,—from eructations, a sense of pressure, of tension, 
or of pain in the epigastrium, or of nausea, etc. Sometimes flatu¬ 
lence is the chief complaint. Easily aroused and excessive peris¬ 
taltic activity may cause attacks of diarrhea on slight provocation ; 
spastic disturbances of stomach and intestines may cause severe 
pains, and, especially in the latter, may give rise to what Kussmaul 
calls “ tormina ventosa.” One sometimes may find a part of the 
alimentary canal distended by gas and giving for the moment the 
impression of a tumor. I believe that the much-talked-of diabetic 
crises gastriques usually are of spastic nature. They may be quite 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 10 J 

painful and be followed by diarrhea, and in rare cases by vomiting. 

I can not find that they differ from similar manifestations in purely 
neurasthenic cases, and they certainly resemble these more nearly 
than the tabetic “ crises gastriques,” to which they have been com¬ 
pared. 

Secretory neuroses certainly exist much oftener than they are 
noted, being sometimes difficult of detection, even on elaborate in¬ 
vestigation. I have twice seen in diabetic patients what I believed 
to be an excessive secretion of gastric juice, a condition that is sel¬ 
dom mentioned. The glycosuric dystrophy is rather likely to 
diminish the secretions, but an exception in the other direction may 
occur with the gastric juice, just as sometimes hyperhidrosis is 
observed instead of the customary anhidrosis. Hyperacidity (from 
hydrochloric acid) has sometimes been noted (Riegel, Naunyn). I 
believe that it is not uncommon. 

The most serious of all gastric neuroses that can attack the dia¬ 
betic patient is nervous anorexia (Gull, Lasegue), which is some¬ 
times found in neuropathic persons, but which, happily, is rare both 
in association with and independently of diabetes. In the few 
cases other than of diabetes in which I have encountered this 
curious affection—which has little in common with the refusal to 
eat in developed mental diseases—the course has been favorable, 
and the patients, after a few weeks of marked inanition, have been 
restored to normal appetite and health. This seems also to have 
been the almost universal rule in recorded cases. In diabetic 
patients, however, the prognosis appears to be much less favorable. 
The anorexia is sometimes particularly obstinate, and is especially 
pronounced with regard to meat and fat, and even if the patient is 
allowed a completely unrestricted diet,—which, I think, is to be 
recommended,—all remedies may fail to secure the ingestion of 
more than a small part of the food required for the genera¬ 
tion of the necessary number of calories. Most of these patients 
are women. The last one under my care exhibited after the begin¬ 
ning of the anorexia no glycosuria, but pronounced diaceturia 
from the inanition, and died after several months of marasmus. 

Gastro-intestinal changes have often been found after death, 
though they are rarely of a marked nature. The increased diges- 


io8 


DIABETES MELLITUS AND GLYCOSURIA. 


tive demand causes at first functional hypertrophy in different 
structures. Dittrich, Frerichs, Lancereaux, Rosenstein, and others 
found hypertrophy of the muscular layers in the stomach. Boccardi 
saw (in diabetic dogs) enlargement of the gastric glands and their 
ducts, and dilatation of the lymphatic vessels. [Hyperacidity of the 
gastric juice—0.4 per cent.—is not rare (Riegel).] Boccardi also 
found Brunner’s glands and Lieberkuhn’s crypts hypertrophied. 
I have generally found, both clinically and after death, a rather 
large, but never decidedly dilated, stomach. I have several times 
on postmortem examination seen enlargement of the mesenteric 
glands, as first pointed out by Frerichs. 

In advanced cases there is atrophy both of the muscular (Fre¬ 
richs) and of the glandular elements (Ferraro, Boccardi). Armanni 
found in one of Cantani’s patients pronounced atrophy of the 
peptic glands. Rosenstein mentions a decreased amount of hydro¬ 
chloric acid. These changes and those that sometimes occur in the 
pancreas suffice to explain the severe digestive troubles in Hirsch- 
feld’s cases, previously mentioned. Catarrhal changes are exceed¬ 
ingly common. 

Hemorrhage and ulceration are mentioned as occurring in 
different parts of the gastro-intestinal tract (Frerichs, Ferraro, and 

The pancreas plays a most important part in the pathogenesis 
of diabetes mellitus, and I propose further on to describe pan¬ 
creatic diabetes and to give a summary of v. Mering’s and Mink¬ 
owski’s discovery of the results of extirpation or resection of the 
pancreas. 

Clinically, anything noteworthy with regard to the pancreas is 
found with comparative rarity among diabetic patients. As I 
write, it happens that I have under observation such a case, in which 
the rapid development from day to day is striking. The patient, a 
Jewess, sixty-seven years old, has had upward of six per cent, of 
glucose in her urine, the sugar disappearing entirely with restriction 
of diet. In the beginning of the diabetes, which set in quite sud¬ 
denly, there was no diacetic acid in the urine. Now, Gerhardt’s 
reaction is pronounced as a result of inanition. The patient is 
often ravenously hungry, but can scarcely take any food when it 



SYMPTOMS AND COMPLICATIONS OF DIABETES. IO9 

is brought to her. She sometimes vomits, and complains often of 
severe pains in the epigastrium and in the back. Palpation raises a 
suspicion of increased resistance over the head of the pancreas. 
No icterus is present, but a decided cachectic hue. The feces some¬ 
times contain large quantities of fat. Unfortunately, I shall not 
be able to be present at the postmortem examination, which is cer¬ 
tain to take place within a few weeks, and which probably will 
reveal a carcinoma of the pancreas.* 

Since the connection between diabetes and disease of the pan¬ 
creas was pointed out that organ is as much studied in diabetic 
patients after death as it was neglected in the past. Such changes 
in the pancreas as can be reasonably considered to have caused the 
diabetes are, however, found comparatively rarely—certainly not in 
more than ten per cent, of all autopsies after diabetes. In fully 
ninety per cent, or more of such cases the pancreas is either normal 
or diminished in size and flabby in consistence, with small but 
otherwise normal acini; it presents a condition of simple atrophy, 
which may with much better reason be considered an effect than a 
cause of the glycosuric dystrophy, f 

Among the comparatively few cases in which disease of the pan¬ 
creas may be considered as a cause of the diabetes the most com¬ 
mon are atrophy and cirrhosis from the presence of calculi in the 
ducts, which may, in consequence, be much enlarged. 

Cirrhosis of the pancreas, interstitial pancreatitis, may also exist 
without the presence of calculi (Heinemann), and in exceptional 
cases may cause diabetes. 

Sometimes the pancreas is the seat of more or less fatty necrosis, 
as I have seen in cases in which the whole clinical picture has been 
that of fat, constitutional, gouty, nonpancreatic diabetes. Seyler 
recently recorded a case of ischemic fatty necrosis, which he con¬ 
sidered due to atheromatous processes that were exceedingly pro¬ 
nounced in the celiac axis and its branches, with diabetes as a 
remote sequel. 


* Since this was written the diagnosis has been found to be correct. It is a curious 
fact that the woman’s father also died of carcinoma of the pancreas. 

f My opinion in this respect is based upon not a few personal autopsies and on infor¬ 
mation gained in Carlsbad, where a considerable number of postmortem examinations 
after diabetes are made. 



I IO 


DIABETES MELLITUS AND GLYCOSURIA. 


Some observers mention interstitial lipoma of the pancreas 
(Hansemann, Naunyn). 

Hyaline necrosis, with homogeneous, transparent contents in the 
enlarged, glandular cells, such as has been described by Armanni 
in the kidneys (see below), seems also sometimes to occur in the 
pancreas (Saundby). 

Carcinoma of the pancreas has several times been found after 
diabetes, and is now and then diagnosticated during life. It may 
exist without diabetes, partly because a sufficient amount of the 
glandular tissue is left intact, partly, as Hansemann points out, 
because of the retention by the degenerated cells of some of their 
functional capability. 

Other changes in the pancreas are rare. Abscess has been 
found, but seems only exceptionally to have time before death to 
cause diabetes. Cysts generally leave enough of normal tissue to 
prevent the development of diabetes. Frerichs has reported a case 
in which the postmortem findings seem to indicate the development 
of diabetes as a result of (Fitz’s) hemorrhagic acute pancreatitis ; 
Benda and Stadelmann have reported a similar case. The majority 
of instances of acute hemorrhagic pancreatitis are unattended with 
glycosuria (Seitz). 

Hansemann * has recently published an excellent paper on the relations of 
the pancreas to diabetes. He believes—on insufficient grounds, it seems to 
me—in the occurrence of a specific variety of diabetic atrophy of the pancreas, 
and maintains that there exist anatomic differences between this and a simi¬ 
lar state after nondiabetic cachexia or marasmus. 

The liver is the organ in which one must look for the immediate 
cause of diabetes if, with Bernard and his many adherents, one 
considers the condition to depend upon an excessive production 
of sugar. We have already seen that a number of affections of 
the liver are sometimes, though inconstantly, accompanied by 
glycosuria, which may or may not be found after ligation of the 
gall-ducts, or, together with biliary fistulae, after attacks of gall- 
stones, after trauma over the liver in association with pylethrom- 
bosis, organic heart-disease and a consequent stasis in the liver, 
acute yellow atrophy, phosphorus-poisoning, amyloid degeneration, 


* “ Zeitschr. f. klin. Med.,” 1894. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 


I I I 


and, above all, cirrhosis. I consider the frequency of the associa¬ 
tion of cirrhosis of the liver and glycosuria fully demonstrated since 
Naunyn, in his excellent work recently published, mentions 22 
cases of incipient and 2 cases of advanced cirrhosis of the liver 
among 152 diabetics. 

Still, it must not be expected that some distinct abnormity of 
the liver will be found clinically in a large percentage of diabetic 
patients. The character of Naunyn’s figures depends on the 
enormous frequency of cirrhosis of the liver in and around Stras- 
burg, where his observations were made ; his earlier figures are 
much lower. The usual state of the liver is, so far as clinical 
investigation goes, a normal one. On percussion the size of the 
organ is found to be within the normal limits, and palpation yields 
no information of any change in form, consistency, or sensibility. 
In other cases, fewer though not very rare, there is some enlarge¬ 
ment and perhaps some tenderness on pressure.* 

Now and then any one who sees many diabetic patients will find 
one with a cirrhotic liver—generally of the usual atrophic variety. 
I will cite two cases under observation within the last few years : 

Dr.-, a Scandinavian, is an unmarried physician, fifty-four years old, 

who has a great aversion to pure water. He does me the honor to consult me in 
Carlsbad, where he appears in my office with watery eyes, a rough voice, trem¬ 
bling hands, and a flabby panniculus, and complains bitterly of loss of appetite 
and nausea, especially in the mornings, etc. When he discovers that I have, 
without asking any unpleasant questions or making further investigation, 
booked him as a case of chronic alcoholism, he indignantly protests, exclaim¬ 
ing that he has drunk “ only ” a bottle of claret and half a bottle of whisky a 


* Glenard, of Vichy, has arrived at other conclusions in his “ Resultats Objectifs 
d’Exploration du foie chez les Diabetiques,” Paris, 1890. Among 324 diabetics he found, 
on palpation, by a method that he designates “ procede du pouce,” a distinct change in 
60 per cent., and these cases he classifies under 8 varieties and 42 subvarieties, which 
he illustrates by diagrams. So far as both classification and palpation go, this is entirely 
beyond me, as well as some others. The last medical friend to whom I showed Glenard’s 
plate did as Voltaire’s governor—“ il releva sa moustache et sourit amerement,” but said 
nothing. Neither will I concede, without all reservation, the truth of Glenard’s state¬ 
ment : tout foie percu par la palpation chez le vivant est un foie anormal. Glenard con¬ 
siders hypertrophy of the liver to be present in 34.5 per cent, of all cases of diabetes, 
and usually limited to the right lobe; the consistency to be increased in one-third and 
sensitiveness in one-fourth of all cases ; and nontender induration to be present in 23 per 
cent, of all cases and in 40 per cent, of those in which the liver can be felt by palpa¬ 
tion. 


/ 




I 12 


DIABETES MELLITUS AND GLYCOSURIA. 


day. Even this concession probably represents only a part of the truth. 
Syphilis was denied. 

The radial and the temporal arteries were sclerotic. The heart was 
somewhat enlarged in all directions ; the second aortic sound somewhat accent¬ 
uated. On percussion the right lobe of the liver appeared to be distinctly 
diminished in size, but there was no tenderness. The spleen was a little 
enlarged. There was no icterus, no bile in the urine, and no manifestations 
of stasis. The tongue and the breath were fairly normal; only a few teeth 
remained, and those were carious. 

The patient was irritable, slept badly, and could not approach steep declivi¬ 
ties. Sexual power was “ highly satisfactory.” The knee-jerks were normal. 

When the patient received about 120 grams of starch with his food, he 
passed 1700 cu. cm. of urine of a specific gravity of 1.019 and containing a 
trace of albumin and about 0.05 per cent, of glucose. On microscopic exami¬ 
nation quite a remarkable number of calcium-oxalate crystals were found, and 
only a few hyaline casts. Single samples of the urine contained as much as 
0.5 per cent, of glucose. Glycosuria was first observed fourteen years ago. 

The patient died about a year after my examination, and I received word 
that the liver was fairly well advanced in cirrhosis. 

Mr.-, a Jewish Bavarian brewer, thirty-nine years old, whose father had 

been a diabetic and who himself had always been “ nervous,” forgot the law 
and the prophets and the usually temperate Jewish customs, drank for many 
years much “ Kornbranntwein ” and beer, smoked ten cigars a day, and was 
far from moderate “in puncto sexus.” He insists that he never had syphilis. 
Two years ago he began, from mere thirst, to attack the beer-casks even more 
energetically than before, and his physician found four per cent, of glucose 
in the urine. Since then the patient has lived under a moderate restriction of 
carbohydrates. 

The man was exceedingly neurasthenic, and had a “ smoker’s heart.” The 
reflexes were normal. The breath was natural; one tooth was missing, and the 
remainder presented very little caries. The liver was somewhat reduced in size. 
The left lobe was distinctly palpable. The spleen extended a little beyond the 
anterior axillary line. Slight icterus existed. About 120 grams of carbo¬ 
hydrates caused scarcely 0.5 per cent, of glucose to appear in the daily 2500 
cu. cm. of urine, with a specific gravity of 1.016 and containing a trace of 
albumin. 

I have already mentioned the frequency with which gall-stones 
complicate diabetes mellitus. 

On postmortem examination the liver often appears normal to 
the naked eye and on microscopic examination. In other numer¬ 
ous cases the liver is slightly enlarged, probably as a result exclu¬ 
sively of dilatation of the vessels. The hyperemia is of the active 
kind. The veins usually are not distended, but the arteries and 



SYMPTOMS AND COMPLICATIONS OF DIABETES. I 13 

capillaries are distinctly so, and the organ presents a more or less 
rosy color, often limited to certain parts. In some cases the vessels 
may be dilated “ ex vacuo as a result of atrophy of the liver-cells 
(Armanni). Now and then one finds what Hanot has described as 
a liver “ couleur chamois,” with a reddish-yellow color, and the 
intralobular veins distended. Simple atrophy, with diminution in 
size and a brownish-yellow color, is not rare. The same can be 
said of the typical fatty liver. Under these conditions the gly¬ 
cogen, which is always likely to be diminished, especially in cases 
of severe glycosuric dystrophy, reaches its lowest figures (Boc- 
cardi). Cirrhosis, moderately developed, is not rare, but rarer than 
any of the other states mentioned. Abscess, probably somewhat 
more frequent in association with than independently of diabetes, 
is, nevertheless, quite exceptional. When the fatal issue has been 
immediately preceded by high fever, the parenchymatous change 
designated by the Germans as cloudy swelling is found in cases of 
diabetes, as under other conditions. 

Boccardi observed in dogs, after extirpation of the pancreas, 
hyperemia of the liver, but no true hypertrophy. Atrophy or 
fatty degeneration quickly came on. While the nucleus remains 
perfectly visible, vacuoles are discernible in the protoplasm, as after 
arsenical poisoning (Steinhaus, Gianturco, Sampacchia). The vessels 
become markedly dilated, partly, at least, in consequence of an in¬ 
fluence “ ex vacuo and small hemorrhages occur, especially near 
the surface. Boccardi found also in the liver diabetic desquamative 
endarteritis, but not the hyaline necrosis observed in the spinal cord 
(Boccardi), in the kidneys (Armanni), in the pancreas (Saundby), 
and in the liver (Ferraro). 

Roque, Devie, and Hugonenq found here and there among the liver-cells 
crystals which they believed to be leucin or tyrosin. 

Bonome,* after extirpation of the celiac ganglion, noted neuro¬ 
paralytic dilatation of the vessels and hemorrhage and atrophy of 
the lobules ; i. e ., a state similar to which Boccardi found in the 
liver of dogs after extirpation of the pancreas. 

The spleen may be mentioned here on account of its relation to 


* “ Riforma Med.,” 1842. 




DIABETES MELLITUS AND GLYCOSURIA. 


I 14 

the liver. It is, like all the abdominal organs, often hyperemic and 
somewhat enlarged. Clinically, distinct enlargement is of import¬ 
ance, as it may strengthen a doubtful diagnosis of incipient cirrhosis 
of the liver. In advanced diabetic marasmus the spleen is often small 
and flabby, and it participates in the general atrophy. 


Urinary Organs. 

The kidneys are often slightly changed in diabetes, but compara¬ 
tively rarely show excessive alterations. 

Fully a third, perhaps more, of all diabetic patients show albu¬ 
minuria. The albumin in most cases is present only in traces, or 
at least in small quantities, and it usually does not reach so much 
as one part in a thousand. Almost all patients, who have lived 
for some time within the severe stage, present some albumin¬ 
uria, which in the mild stage occurs only in a small minority of 
cases. 

Slight albuminuria in a diabetic patient is usually considered of 
less clinical and prognostic significance than under other conditions; 
and in the presence of conflicting therapeutic indications, as between 
the kidneys and the glycosuric dystrophy, physicians generally 
regard chiefly the latter. In some cases the albuminuria is an 
effect of stasis in the kidneys from the weakness of the heart that 
is common among diabetics. In cases that have reached the severe 
stage it is often undoubtedly of toxic origin, resulting from the 
irritation of the kidneys in consequence of the “acidosis.” Arterio¬ 
sclerosis per se also not rarely causes some degree of albuminuria 
without the presence in the urine of epithelial elements from the 
kidneys ; such vascular changes are likely to be found earlier in 
life in diabetics than is usual in others. Further, true nephritis is 
not rare in diabetes. As Grube correctly remarks, it is usually a 
form of mixed parenchymatous and interstitial character ; casts can 
then usually be found without difficulty in the urine. (From the 
presence in the urine of hyaline casts no conclusions as to more 
profound alterations are to be reached, as such formations are 
extremely common, especially in senile individuals, in connection 
with or independently of true nephritis.) The typical gouty 
kidney is occasionally found. It sometimes causes no albuminuria, 


SYMPTOMS AND COMPLICATIONS OF DIABETES. I I 5 

but only polyuria, the urine being of low specific gravity, and 
containing only small quantities of glucose. 

Like almost all writers on diabetes, I have a number of times 
observed the curious change in the glycosuria that takes place in 
cases with cirrhotic processes in the kidneys. As the arterial 
pressure and the quantity of the urine increase and the specific 
gravity falls with the advancing cirrhosis, the glycosuria ceteris 
paribus slowly but quite considerably grows less marked. The 
same patient that in the incipient stage of interstitial nephritis with 
a fixed supply of carbohydrates excreted twenty grams of glucose 
in the twenty-four hours, may five years afterward, under the same 
conditions, excrete only one gram of glucose. Such cases may 
finally resemble the rare combination of diabetes insipidus with 
insignificant but pathologic traces of glucose in the light, abundant 
urine. The state of the glycemia in these cases can not at present 
be considered settled, and the result of injections of phloridzin 
in patients with interstitial nephritis is still uncertain (Klemperer 
versus Magnus-Levy, Naunyn, and others). Naunyn, in his recent 
work, expresses the opinion that the curious increased tolerance 
for carbohydrates in cases of diabetes complicated with chronic 
interstitial nephritis is only an analog to the same tolerance 
observed in all cases in which diabetes is associated with some 
other severe organic disease attended with cachexia and marasmus. 
Still, I have seen cases in which the cirrhotic process in the kidneys, 
though developed, has left a fairly good general state of health, 
and in which this increased tolerance has been perfectly evident. 
Concerning the influence of the kidneys on glycosuria, reference is 
made for further particulars to what is said in chapter hi on renal 
glycosuria. 

Diabetics are often gouty, and gouty patients often suffer from 
renal calculi, which are not rare in diabetes of the mild “lithemic ” 
type. Budde found 28 cases of nephrolithiasis among 256 
diabetics. 

Otherwise, diseases of the urinary organs do not occur much 
more frequently among diabetic patients than among others. 
Schmitz, who sometimes gathered amazing statistics, quite in¬ 
correctly mentions cystitis as a common complication. Senator, 
Fr. Muller, Guiard, and others have seen pneumaturia; Ernst, 


Il6 DIABETES MELLITUS AND GLYCOSURIA. 

Naunyn, and Hartge have found microorganisms (Ieptothrix, sar- 
cina) in different parts of the urinary tract. Such vegetations easily 
occur in places in which the sweet urine comes in contact with the 
air, but the germs do not, as a rule, spontaneously ascend the 
urethra, and complications of this kind are comparatively rare. 

The kidneys show after death distinct and frequent, but not con¬ 
stant and not marked, changes. With the naked eye generally 
some enlargement and hyperemia of the whole organ is appreciable. 
On section the cortex often presents some slight fatty and opaque 
change of color; and the glomeruli are enlarged, while the 
medulla is distinctly hyperemic. Next in frequency to these con¬ 
ditions the kidney is found without distinct changes. Advanced 
parenchymatous or interstitial alterations are exceptional. The 
nephritis of diabetics usually represents a slight development of 
morbid processes both in the interstitial and in the parenchymatous 
(epithelial) tissue. Sometimes changes like those of the large 
white kidney are seen, but I know of no typical case of this kind. 

Under the microscope some degree of fatty degeneration may be 
found, especially marked in the convoluted tubules, but only rarely 
developed to such a degree as to obliterate the nuclei or other¬ 
wise to compromise the integrity of the cells. 

Fichtner, in 1888, described the curious appearance of a trans¬ 
verse section of the convoluted tubules showing large particles of fat, 
arranged like a string of pearls, in the degenerated epithelial cells 
along the basement membrane. Besides, fatty particles are found 
strewn all over the section of the cells, which, however, almost 
always retain their structure. 

The most characteristic (frequent, but not constant) microscopic 
change is represented by what Armanni * designates hyaline meta¬ 
morphosis, Ebstein hyaline necrosis, and Straus vitreous degenera¬ 
tion. I believe that all these designations denote the same thing, 


* Armanni was the first to describe this curious change, which he considered a meta¬ 
morphosis of leukocytes that had entered the tubes : “ II est peu probable qu’il s’agisse 
d’une metamorphose speciale des Elements epitheliaux,” he says in the French edition of 
Cantani’s work. The Germans were the first to interpret correctly the change as one of the 
epithelial cells. See the works of Frerichs, Straus, Martlien, Albertoni and Pisenti, 
Trambusti and Nesbi, Ferraro, Obici, Boccardi. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. II7 

which also is identical with what Frerichs and Ehrlich described as 
enlarged, polygonal, hyaline, epithelial cells, as found in Henle’s 
tubes. Frerichs and Ehrlich did not, however, consider the change 
a necrosis, the nuclei in their cases always retaining the property of 
taking the stains distinctly. They laid especial stress on the brown 
reaction with Lugol’s solution, distinct even to the naked eye, 
especially in the limiting zone, in the section of the kidney, and de¬ 
noting marked infiltration with glycogen. Later investigations leave 
scarcely any doubt that the hyaline metamorphosis that is probably 
found in several organs besides the kidneys, and perhaps even apart 
from diabetes, is an independent occurrence, and may exist without 
any infiltration with glycogen, which substance, however, seems to 
have a predilection for the altered cells in the loops of Henle. 

Marthen * noted that van Gieson’s stain (hematoxylin and picric acid) col¬ 
ored the hyaline contents of the enlarged polygonal cells a vivid red. Alber- 
toni and Pisenti observed hyaline metamorphosis in dogs, both in the straight 
tubes and in the convoluted tubules, after large doses of acetone (?); and Tram- 
busti and Nesbi noted the same conditions after continued large doses of 
phloridzin. Pisenti and Acri, according to my opinion without sufficient rea¬ 
son, distinguish between Armanni’s hyaline metamorphosis, which they con¬ 
sider identical with Frerichs’ and Ehrlich’s cells with intact nuclei in the isth¬ 
mus of Henle’s loops, and Ebstein’s hyaline necrosis in the convoluted tubules, 
which disintegrates the nuclei of the cells. 

Boccardi often found the kidneys normal in dogs that became 
diabetic after extirpation of the pancreas, but sometimes found the 
vessels and the tubules dilated ; the interstitial tissue somewhat in¬ 
creased, least in the cortex, most in the limiting zone ; Bowman’s cap¬ 
sules with thickened epithelium, desquamation of the endothelium, 
and immigrated white blood-corpuscles ; glomeruli either enlarged 
or atrophic ; epithelial cells in a state of fatty degeneration, which 
sometimes went so far as to disintegrate ; hyaline degeneration with¬ 
out any glycogenic infiltration in 3 of 40 cases ; in the arteries 
the adventitia thickened and the intima exfoliated. 

The sexual organs in cases of diabetes often undergo functional 
and other changes. 

Impotence has already been mentioned among the nervous symp- 


* “ Arch. f. path. Anat.,” 1895. 



I 1 8 DIABETES MELLITUS AND GLYCOSURIA. 

toms. It is rarely absolute, apart from advanced senility; but 
“ facultas cceundi ” is often distinctly weakened from the moment 
the glycosuric dystrophy, however mild, makes its appearance. In 
rare cases sexual vigor remains normal. 

Sterility is common and does not depend on “ impotentia coeundi,” 
as it exists also in women. The cause must rather be looked for 
in some influence exerted by the excess of sugar or by toxins in 
the blood, on the sperm and on the ova, or in atrophy of the testi¬ 
cles, or the ovaries, or in the diabetic metritis of which Lecorche 
speaks. Still, both diabetic men and women may produce chil¬ 
dren, and sometimes conception takes place even in the severe 
stage. Pregnancy in a diabetic woman is often interrupted by mis¬ 
carriage in the fourth or fifth, or as late as the seventh, month 
(Seegen, Gaudard). Further, pregnancy, which sometimes per se 
causes glycosuria or true diabetes, often accelerates the progress of 
an existing diabetes. The mortality among both mothers and new¬ 
born children is very great. Of the latter, 41 in every 100 die soon 
after birth (Gaudard). 

I have seen two cases of diabetes in which orchitis appeared as 
a complication without obvious cause. 

Those parts of the diabetic patient’s skin that often are moist¬ 
ened by the sacchariferous urine readily become the seat of vege¬ 
tation for a small flora of low fungi, which cause eczema, excori¬ 
ations, pruritus, and, especially in the labia majora, sometimes a 
series of furuncles. Vulvitis in women, balanitis , balanoposthitis, 
and sometimes phimosis in men, are induced, and recur readily if 
not restrained by the use of antiseptic lotions. Both in men and 
in women the irritation thus caused gives rise to the development 
of papillomatous excrescences, which are known to have changed 
into epitheliomata (Naunyn). 

Straynowski mentions atrophy of the uterus and of the ovaries 
as occurring in diabetic women. Analogous changes in the testicles 
may be quite distinct in marantic cases in men. 


Organs of Special Sense. 

Diseases of the eyes are extremely common in diabetics, and there 
is no part of these organs that has not been named as the seat of 


SYMPTOMS AND COMPLICATIONS OF DIABETES. I 19 

pathologic processes caused by the glycosuric dystrophy. Though 
most of these diseases develop only after the diabetes has existed 
for a long time, they not rarely constitute the primary reason for 
the patient’s seeking medical aid, and they thus lead to the dis¬ 
covery of the dystrophy. It has been said that two-thirds of all 
diabetic patients suffer from some affection of the eye. This esti¬ 
mate must certainly be based upon hospital statistics and upon 
observations among severe cases, as in private practice, with its 
large number of mild cases, the proportion is much smaller. All 
the deleterious influences already named as belonging to the gly¬ 
cosuric dystrophy are efficient with regard to the eye, but the 
toxins in the blood in many cases play the most important role; 
and some of the diabetic affections of the eye are very similar to 
those that occur during long-continued poisoning with alcohol or 
tobacco, or to those that may be produced in quite a short time by 
injections into the blood of common salt, sugar, naphthalin, and 
other substances. 

The most frequent diabetic affections of the eye are cataract, 
anomalies of accommodation (especially premature presbyopia ), retin¬ 
itis, and inflammation of the optic nerve. 

Diabetic amblyopia or amaurosis , iritis and iridocyclitis, opacities 
in the vitreous body, processes in the cornea and sclera, paralysis of 
the muscles, and some other dystrophic troubles are less common.* 

Diabetic cataract generally develops after the dystrophy has been 
present for many years, but in exceptional cases and in the specific 
soft form it may appear after a few weeks ; this happens especially 
in children. The affection is almost always bilateral, and is found 
in both stages of diabetes, although it is more frequent in severe 
cases, without bearing any fixed relation to the intensity of the 
diabetes. 

Weir Mitchell caused cataract in frogs by subcutaneous injections 


* For more extensive information on diabetic affections of the eye, reference may be 
made to the works of Leber, Grsefe, Foerster, Jacobson, Wiesinger, Bouchard, Schirmer, 
Knies, Hirschberg, Schmidt-Rimpler, O. Becker, Deutschmann, Berger, Papanikolau, 
and others. The essential facts can be found in the “ Archiv fiir Ophthalmologie. ” The 
notes of my own cases are incomplete with regard to the ocular state, as I always refer 
the patient for this information to the best specialist at hand. 



I 20 


DIABETES MELLITUS AND GLYCOSURIA. 


of sugar; Richardson noted the same result in frogs and fishes by 
keeping them in a dilute solution of sugar; and cataracts have 
since been induced in rabbits and frogs by introducing sugar into 
the fold of the conjunctiva. Thus, there can be no doubt as to 
the efficiency of the hyperglycemia to bring about cataract, 
whether it be due to direct irritation of the tissues of the lens or 
to their desiccation. The cataracts induced artificially begin by 
the formation of vacuoles in the cells ; and this may also be the 
case with diabetic cataract before proliferation and disintegration 
of the cells take place. The diabetic changes in the vessels, with 
local nutritive disturbances, the marasmus, and other common 
influences, may contribute to the result, and may in many cases, 
especially in those not representing the typical diabetic soft cataract, 
be the chief etiologic factors. The hypothesis of the formation 
of lactic acid in the aqueous humor of the eye has been abandoned, 
since investigations have proved this liquid always to be alkaline. 
In the liquids of the eye, in the lens, and in the vitreous body, 
where glucose also has been found apart from diabetes, this sub¬ 
stance seems to be increased when diabetes develops (Deutsch- 
mann, Gorlitz, Hedon and True). 

Typical diabetic cataract, which is the customary variety in 
young persons with severe diabetes, is of the soft kind. The 
process begins, according to Knies, in the small polygonal cells on 
the posterior aspect of the anterior part of the capsule of the 
lens; the adjacent cellular elements of the lens next begin to 
undergo changes. Becker states that opacities appear at first in 
the equatorial zone, then in the posterior, and afterward in the 
anterior, cortical substance. Whether the first change begins 
behind or in front, it is certain that, contrary to what takes place 
in the common senile cataract, the most superficial parts of the 
cortical substance are the first to undergo change in the develop¬ 
ment of the typical diabetic cataract. The first macroscopic mani¬ 
festation of this is the appearance of a milky layer in the field of 
the pupil; then the whole mass of the lens whitens, and mother-of- 
pearl-like patches become visible therein. The entire development 
and appearance of this typical, soft, diabetic cataract strongly 
resemble what Bouchard has described in speaking of the experi¬ 
mental cataract caused by naphthalin. 


SYMPTOMS AND COMPLICATIONS OF DIABETES. I 21 

The soft cataract is, however, by no means the only variety 
found in diabetic patients, and so far as my experience goes, it is 
not even the most frequent. In elderly diabetics one often finds 
the usual variety of senile cataract, with central, yellowish sclerosis, 
and bluish-gray, radial streaks between this and the still normal 
peripheral parts of the lens and (before the maturity of the cataract) 
the shadow of the iris, etc. There is good reason to believe that 
these changes are favored by the glycosuric dystrophy, and that 
they, like diabetic gangrene, are an expression at the same time of 
diabetes and of senility. 

Konig found among 500 diabetic patients only 10 cases of cata¬ 
ract. Most other writers made the proportion higher. I have 
certainly seen more than 10 cases of cataract in association with 
diabetes, though I have not yet reached 500 cases of the latter. 
This may be due partly to the fact that several cases from Dr. 
Nordenson’s extensive clinical material have been referred to me in 
Stockholm. I suppose that among diabetic patients in Carlsbad 
from three to four per cent, exhibit cataractous changes. 

Sometimes, and especially in severe cases of diabetes, one finds 
that the visual near-point, even in young persons, grows more and 
more remote, and that premature presbyopia develops. This con¬ 
dition has been attributed to marasmus, with its weakening influ¬ 
ence on the muscles of accommodation, to alterations in the vessels, 
to neuritic processes, and to hemorrhages. Diminished elasticity 
of the lens may also be a contributing cause. 

Mydriasis may arise from toxic influences. In the presence of coma the 
sphincter of the pupil may be seen to resist and to react in quick succession to 
the paralyzing influence of the poisons in the system. Still, the pupils in dia¬ 
betic persons may be large altogether independently of diabetes—“ Cette dilata¬ 
tion des pupilles, associee le plus souvent aux symptomes de depression est un 
bon signe des etats neurastheniques,” says Bouveret (“ La Neurasthenie ”). 

Myopia from the tumefaction of the lens is the most frequent anomaly of 
accommodation in cases of diabetes, if it develops in middle age or later. This 
fact should be borne in mind, and the urine in such cases of myopia should 
always be examined for glucose. 

Hypermetropia is mentioned by Horner as occurring in associa¬ 
tion with diabetes. 


9 


122 


DIABETES MELLITUS AND GLYCOSURIA. 


Diabetic retinitis (elaborately described by Hirschberg) belongs 
in general to one of two groups, and may be either exudative or 
hemorrhagic. 

Exudative diabetic retinitis—retinitis diabetica centralis punctata — 
presents small, glossy, nonpigmented exudations around the 
central portion of the retina. The exudates have uneven borders 
without being so distinctly stellate as the exudates of albu¬ 
minuric retinitis ; here and there a small point of blood may be 
visible. There is no discoloration of the papilla ; if there is, a 
renal complication and albuminuric retinitis should be suspected. 

Hemorrhagic diabetic retinitis is characterized by the presence of 
a number of ecchymoses of varying size distributed over the retina. 
They sometimes cause amblyopia and occasion quite a dubious 
prognosis, as they often represent only a part of hemorrhages 
extended over different regions of the central nervous system. I 
have seen them attended with serious symptoms, sometimes even 
with perfect loss of consciousness. They often occur successively 
over some length of time, and they may be found in all stages in the 
same eye, as recent hemorrhages and as whitish residual patches. 
I consider these small retinal hemorrhages as analogous in type to 
the small hemorrhages in the brain, which I suspect to be frequent 
in inveterate cases of diabetes, and which often may be unattended 
with manifest symptoms. 

Diabetic optic neuritis is so much like the neuritis due to alcohol 
or tobacco that its diabetic nature has been called in question even 
in recent times {e.g., by Mauthner). Still, Schmidt-Rimpler found 
this complication in 34 among 140 cases, and Leber in 14 among 
50 cases of diabetic disorders of the eye, and it can not be doubted 
that inflammation of the optic nerve is not uncommon in inveterate 
cases of diabetes independently of both alcohol and tobacco, 
though it often escapes detection. When developed, it presents a 
central scotoma, with deficient color-perception, corresponding to 
the macular part of the optic nerve, and a whitish discoloration 
of the temporal part of the papilla. The differentiation from 
neuritis due to alcohol or tobacco can be made only from the his¬ 
tory ; in some cases all three causes may contribute to the result. 
Peripheral contraction of the field of vision and atrophy and dis- 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 123 

coloration of the entire papilla may ensue. Diabetic optic neuritis, 
though it often exhibits temporary improvement, has a worse prog¬ 
nosis than the analogous affections caused by alcohol or tobacco, 
which, as is well known, are themselves quite obstinate, even after 
the removal of their causes. 

Amblyopia and amaurosis may arise in the course of diabetes 
from such alterations within or without the eye as ordinarily give 
rise to them, but they may also result from the action of diabetic 
toxins (Leber). In the latter event the danger of coma is never to 
be lost sight of. In the last case of this kind that I have treated 
exceedingly elaborate investigation by Dr. Nordenson failed to dis¬ 
close any other than a toxic cause ; the deflection of the ray of 
polarized light to the left, due to / 3 -oxybutyric acid in the urine, 
equaled a little more than 0.5 degree with Hoppe-Seyler’s instru¬ 
ment. The patient died about two months afterward in coma. 

Diabetic iritis * is a torpid, suppurative process without ulceration 
of the cornea ; it usually appears in both eyes, and is observed in 
advanced cases. Leber noted hypopyon in two among nine cases. 
A fibrinous deposit over the whole pupil was present in several 
cases, but disappeared quickly and completely under the influence 
of sodium salicylate. In some cases only an adhesive iritis is 
found, with synechiae. Finally, there seems to exist exceedingly 
torpid forms of the disease, which develop almost imperceptibly 
until they cause a change in the color of the iris. The whole pro¬ 
cess may lead to atrophy of the iris, sometimes to glaucoma. 

The choroid may participate in the process and cause opaci¬ 
ties in the vitreous body. Leber observed detachment of the 
choroid. 

Hemorrhages and opacities in the vitreous body have their origin 
in the retina or in the choroid. 

Diabetic keratitis presents itself as a parenchymatous inflammation 
of neuroparalytic character, and may lead to ulceration and 
suppuration. 


* Leber, “ Arch. f. Ophthal.,” 1885. 



124 


DIABETES MELLITUS AND GLYCOSURIA. 


Scleritis and episcleritis are also mentioned, but their relation to diabetes 
seems undecided. 

The eyelids may become the seat of hordeolum , chalazion , 
eczema , or herpes . Hemorrhages in the conjunctiva are considered 
to be an effect of diabetes and a special reason for analysis of the 
urine. 

The intracranial hemorrhages that are likely to complicate dia¬ 
betes of long standing sometimes cause paralysis of the muscles of 
the eye , and any one that has seen a large number of diabetic 
patients must also have seen such disturbances of function on the 
part of the abducens, the oculomotor, the trochlear, or the facial 
nerve, with strabismus, lagophthalmos, ptosis, etc. In some cases 
rapid absorption and complete restitution take place. I have also 
seen paretic symptoms remain for several years and for the re¬ 
mainder of the patient’s life. 

Being constantly on the alert for the many severe diseases of the 
eye that threaten the diabetic patient, one is likely to overlook 
symptoms of a purely neurotic and less dangerous nature. If, how¬ 
ever, the physician makes it his custom to ask concerning such 
symptoms, and sometimes even if he does not, he will gain infor¬ 
mation indicating the frequency, also in this field, of neurasthenic 
symptoms in cases of diabetes. The practitioner who is not well 
versed in the use of the ophthalmoscope will often find difficulty 
in excluding organic disease. Sometimes neurasthenic asthenopia, 
with local subjective sensations and deficiency of endurance in the 
use of the eyes, is observed. Many diabetics display marked hyper¬ 
esthesia for light. 

Diseases of the ears * are much rarer complications of diabetes than 
diseases of the eyes. Central disturbances of the acoustic nerve, 
whose center is quite near to the situation of Bernard’s puncture, 
are exceedingly rare. 

Otitis follicularis externa , or furuncle of the external auditory 


*See Kuhn, “ Archiv f. Ohrenkr.,” Bd. xix ; Kirchner, “ Deutsche med. Wochen- 
schr.,” 1887 ; KSrner and v. Wildt, “ Zeitschr. f. Ohrenheilk.,” Bd. xxm. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. I 25 

canal, is undoubtedly more common in diabetics than in other indi¬ 
viduals. 

Otitis media diabetica sometimes leads to suppuration of the 
internal ear and its osseous parts, and one now and then sees 
patients with scars after operations in the mastoid region. Inflam¬ 
mation of the middle and internal parts of the ear may cause 
meningitis, but few such cases are recorded ; and these processes in 
the ear, which owe their origin to bacteria (streptococcus, staphylo¬ 
coccus, etc.), scarcely occur in more than one per cent, of all cases 
of diabetes. 

I have had under observation a rare and interesting case of trauma of the 

inner ear in a case of diabetes. Mr.-, a Scandinavian merchant, sixty- 

six years old, had suffered from diabetes for about eighteen years. He was in 
the mild stage of the dystrophy, and the glycosuria disappeared when the car¬ 
bohydrates were restricted to about thirty-five grams. I was called early one 
morning to the patient, who had fallen out of bed during the night, and somehow 
had been struck on the left side of the head by a basin filled with water that 
had fallen over him. The left tympanic membrane had ruptured and the 
pillow was stained with serous liquid slightly mixed with blood. The pulse 
was at least normal in frequency, and thus indicated no irritation of the pneu- 
mogastric nerve. There were no symptoms referable to the eyes, but the 
patient presented a complete inability to maintain equilibrium. I supposed a 
fissure through the labyrinth and the semicircular ducts had taken place. 
During proper local and general treatment the patient otherwise recovered in 
the course of some weeks, but the inability to maintain equilibrium, subsiding 
very slowly, remained for several months. 

Ordinary functional nervous troubles of auditory character are 
not absent. The diabetic patient often exhibits a marked acoustic 
hyperesthesia, which sometimes causes him to make elaborate ar¬ 
rangements to avoid noise. Subjective acoustic perceptions, espe¬ 
cially during the night (tinnitus aurium, etc.), are not rare. Otalgia 
is sometimes complained of. The cause may then be looked for in 
the teeth, which are so commonly carious in diabetes. In other 
cases the otalgia is only a secondary manifestation of an extensive 
neuralgia in the distribution of the fifth pair of nerves (auriculo¬ 
temporal branch), or of neuralgia in the distribution of the occipital 
or the auricularis magnus nerve. The differentiation must then be 
made between a merely nervous and a rheumatic affection. Rheu¬ 
matic infiltrations in the soft parts of the head, which constitute one 



126 


DIABETES MELLITUS AND GLYCOSURIA. 


of the most attractive hobbies of the professional masseur, may be 
the cause. Sometimes pruritus or hyperesthesia or paresthesia of 
the outer ear is spoken of. 

The skin often presents local or general changes. 

General changes are observed in the severe stage or in advanced 
cases in the mild stage. I have already mentioned the diminished 
secretion of the sebaceous and the sudoriferous glands—the astea- 
tosis and the anhidrosis —and the resulting marked dryness of the 
skin. The cause of this condition resides not only in the more 
tenacious retention of the water of the blood within the vessels by 
reason of the hyperglycemia, but also in the atrophy of the skin , not 
rarely found in the severe stage, especially on the hands, and still 
more often in the face, where one observes the change that, in its 
fully developed state, is called “ glossy skin.” The skin is mani¬ 
festly thin, and there is a marked, circumscribed, cyanotic redness 
of the cheeks. 

It is in such cases that diabetic pruritus is best marked. It is 
usually much less intense than in cases of icterus, for instance, and 
it rarely constitutes a serious annoyance. 

I have already mentioned the furuncle, the carbuncle, the “ mal 
perforant” and Raynaud’s disease, the different forms of diabetic 
gangrene and the different forms of eczema, and other changes that 
result when the skin is often moistened by the urine. It is chiefly 
these latter eruptions that the French call “ diabetides,” which 
appellation should not suggest an idea of anything pathognomonic. 

So far as I know, there is not a single change in the skin in 
diabetes that may not occur apart from this dystrophy. This is 
true even of the rare “ xanthoma tuberosum diabeticum,” observed 
hitherto, in all, in about thirty cases. The one case that I have 
seen presented the customary solid, yellowish-red excrescences, as 
large as peas, distributed in considerable numbers chiefly on the 
extremities. They were most numerous over the triceps muscle on 
the upper part of the arms and over the extensors on the lower 
part. A few were to be seen on the flexor aspect. On the legs 
they were exceedingly numerous over the quadriceps femoris, 
especially in the vicinity of the knee-joint. A few were to be 
seen on the outer sides of the calves and on the dorsal aspect of the 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


127 


tibiotarsal joint. There were a few on the shoulders and on the 
neck, and one in the left external auditory canal. Neither in 
their distribution * nor in any other feature could I discover any 
difference from what I have seen of “ xanthoma tuberosum ” 
attending icterus. The patient was a man twenty-eight years old, 
suffering from severe diabetes, without icterus. 

The formations that Kaposi calls “ dermatitis papillosa diabetica ,” with ex¬ 
crescences in patches on an inflamed base, may probably also be seen inde¬ 
pendently of diabetes, in association with which they are extremely rare. 

Besides the skin-diseases already mentioned, diabetic patients 
frequently yield the dermatologist varied clinical material. I have 
seen erythema, urticaria , lichen, acne, impetigo, rupia, herpes (in¬ 
cluding herpes zoster ), pemphigus, pityriasis, ichthyosis, psoriasis, all 
sorts of eczema, petechice. Purpura hemorrhagica (Dujardin-Beau- 
metz) and pityriasis rubra (Harden) have been mentioned. For 
some of these affections we may look to the marasmus as the chief 
cause. In other cases the hyperglycemia may be efficient. In a 
great many instances the connection with diabetes may consist only 
in the angioneurotic constitution common in diabetic patients, who, 
in fact, often mention that they suffered from their cutaneous 
troubles long before glycosuria arose. 

The hair of diabetic patients offers two peculiarities : in conse¬ 
quence of the asteatosis and anhidrosis it is often dry, and therefore 
presents a ragged appearance; and it is often prematurely gray.f 
Diabetes may have some influence in causing baldness, and “ de- 
fluvium capillorum ” is mentioned by more than one writer on 
this subject. Marked effects of this kind are not conspicuous, and I 

* The distinction between diabetic and icteric xanthoma is said to be that the former 
is equally spread over the whole body, while the latter is distributed as in my diabetic 
patient. Kaposi does not acknowledge the existence of a specific diabetic xanthoma. 

f Susruta, about 1200 years ago, mentioned a peculiar, wild appearance of the diabetic 
patient’s hair. I suppose that the gray hair has no direct connection with diabetes, but 
depends on the great emotional sensitiveness common among diabetic patients. The 
curious and sometimes remarkably sudden influence depressing emotions have in this 
respect is well known. Thus, it is related that a Hindu suddenly turned gray just 
before his execution during the great mutiny (“ Ind. Med. Times and Gazette,” 1859) ; 
as did also Ludovico Sforza when he was taken prisoner, and Guarini da Verona when 
he lost his Greek manuscripts. (See H. C. Wood, “Nervous Diseases,” Philadelphia, 

1887.) 



128 


DIABETES MELLITUS AND GLYCOSURIA. 


know many patients who, after long years of abundant glycosuria, 
still keep a luxuriant growth of hair on their heads. 

The nails sometimes show distinct alterations. Paronychia is not 
rare and sometimes causes the nails to fall out. In other cases the 
nails change without any cause whatever discoverable to the naked 
eye. They become thick, brittle, discolored and brownish, markedly 
curved in both directions, and may then fall out. It seems to 
me that this occurs chiefly in inveterate cases complicated with 
gout, and in cases with distinct neuritis. It is certain that such 
changes are not related to the intensity of the diabetes, and one 
often finds the nails on the hands and feet perfect in patients toward 
the close of life after years of the dystrophy in its severe stage. 


Organs of Locomotion. 

The patient in the mild stage of diabetes is generally an indolent 
person, of sedentary habits, to whom the physician must preach 
long sermons as to the utility and the necessity of bodily exercise, 
and whose muscular strength and endurance usually are much 
smaller than seems indicated by his often robust appearance. The 
diabetic patient in the severe stage often drags himself along with 
an unsteady gait, and is made excessively tired by exercise that con¬ 
stitutes a daily salutary habit in healthy persons, but which in some 
cases of diabetes may be sufficient to cause coma. A patient of 
this kind will rise late and go early to bed, and his lassitude , his 
feeling of excessive muscular weahness, will sometimes even keep 
him in bed throughout the twenty-four hours. 

The muscular neurasthenia is partly the cause of the diabetic’s 
constant feeling of tiredness. The dryness of the muscular tissues 
—much dwelt upon by Dieulafoi—probably is an important causa¬ 
tive factor in cases of marked hyperglycemia. The ^excessive 
amount of sugar in the blood in a similar manner also directly 
affects the motor nerves. In marantic cases the muscles often are 
extremely atrophic and reduced to ribbon-like proportions, of 
which no great mechanical effects can be expected. 

The bones in cases of severe diabetes have been found remarkably 
light and porous, and fractures often heal slowly and imperfectly. 
The enormous amount of those salts that enter into the constitution 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 129 

of the bones sometimes found in severe cases (v. Ackeren, Fodor) in 
the urine seems also to denote disintegration in those structures. So 
far as I know, there have been no systematic investigations of these 
processes and of the consequent osteoporosis in diabetes. Charrin 
and Guignard, with many others, accept the existence of this dia¬ 
betic osteoporosis and believe it due to the acidosis. Considering 
that the acids only diminish, but never entirely neutralize, the alka¬ 
linity of the blood, I am more inclined to believe in a general mar¬ 
antic or in a purely trophic influence, analogous to that observed 
by Kassowitz in the bones of rabbits’ legs after section of the sciatic 
nerve. 

As there are to be found all stages between a normal power of 
assimilating carbohydrates and the greatest possible reduction of 
that power, so also, with regard to the general clinical picture, there 
are all possible intermediate gradations between the healthy indi¬ 
vidual and the patient approaching diabetic coma. There are, 
especially, many persons who live on the border-land between what 
may still appropriately be called the mild and the severe stage, 
and there may be only a slight clinical difference between a patient 
who is free from glycosuria during abstinence from carbohydrates 
and one who even under such dietetic conditions excretes a few 
grams of glucose in the course of the twenty-four hours. If, however, 
a patient is selected from the middle of each of the two stages, quite 
marked clinical differences will generally be found between these 
two representatives of the glycosuric dystrophy. 

The history often presents remarkable points of difference. Mild 
diabetes is often discovered by mere accident; e.g. y on examination 
for life-insurance. In other cases neurasthenic symptoms, or some 
local trouble, or some slight signs of dystrophy guide the sus¬ 
picions of the physician in the right direction. The diabetic 
symptoms, if there are any at all apart from the glycosuria, have 
developed gradually, and the dystrophy has only slightly affected the 
patient, who often is unable to give any definite information as to the 
time of the beginning of the diabetes. Severe diabetes—often in a 
short while—changes a state of health into one of marked ill-health, 
and the patient is often able to name at least the month, and some¬ 
times the day, of appearance of the first symptoms. Even in such 


I3O DIABETES MELLITUS AND GLYCOSURIA. 

cases, in which at first restriction of carbohydrates suppresses the 
glycosuria, sudden appearance of diabetic symptoms is an unfavor¬ 
able sign, and makes probable the future development of the severe 
stage of the disease. 

The actual state of the representatives of the two classes men¬ 
tioned usually presents a number of salient points of difference. 
The patient with mild diabetes may, even after years, appear as a 
man of quite fair, sometimes even of florid, health, with a normal 
complexion, a robust form, and active habits. He is sometimes 
troubled with adiposity or with gout, almost always with “ ner¬ 
vousness.” He may, however, perform quite important duties in a 
private or a public capacity, and can easily conceal his diabetes, 
with its insignificant and vague symptoms, from the world. The 
severely affected patient, with acid toxins in the blood,—the “ acid¬ 
osis,”—often manifestly presents evidence of that marasmus which 
constitutes the most essential distinction between severe and mild 
cases. He is generally thin, often extremely so ; his movements 
are weak ; his gait uncertain ; the expression of his face either lan¬ 
guid and drowsy or uneasy, sometimes desperate ; the complexion 
either of a cachectic pallor or marked by an unhealthy cyanotic red¬ 
ness of the cheeks. His mere aspect reveals his serious state, and 
his family and friends, even without recognizing the nature of his 
disease, often realize that his days are numbered. 

Then, the issue in the two stages of glycosuric dystrophy is dif¬ 
ferent. Mild diabetes is in no specific way fatal ; if it does not 
develop into a severe diabetes, the patient will live until stricken 
by some accidental intercurrent or complicating affection, which, 
though perhaps less frequently, may occur apart from diabetes, 
such as acute pneumonia, carbuncle, cerebral hemorrhage, heart- 
failure, etc. Severe diabetes, however, leads to death in most 
cases through a specific complication caused by the presence of 
toxins in the blood. Acetone may exert some slight contributory 
influence ; the diacetic acid and the low fatty acids, by reason of 
their small amounts, can not per se bring about the result. The 
/?-oxybutyric acid, which may be formed in large quantities, is the 
chief factor in the production of the acid diathesis, the “acidosis,” 
and of the final acute poisoning, which, when once begun, gener- 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


13 I 

ally in a short time leads to paralysis of the nervous centers, and is 
known as— 


Diabetic Coma.* 

The development of diabetic coma may be excited by some in¬ 
considerable depressing incident, such as emotion, fatigue, or a 
slight indisposition. A common cause, or, perhaps better, a com¬ 
mon forerunner, of coma is obstinate constipation, which, after coma 
has set in, may give way to profuse fetid diarrhea. Coma is, how¬ 
ever, promoted not only by all depressing influences, but by any 
cause that increases the acid diathesis, the acidosis. Every agency 
that has both these effects is especially dangerous, and I believe 
that the most frequent immediate cause of coma arises from a too 
rigid restriction of carbohydrates, with consequent inanition and in¬ 
crease of diacetic acid and of / 3 -oxybutyric acid in the blood. 

A feeling of extreme weakness, of drowsiness, and of headache 
generally precedes the attack. Sometimes there is complete loss 
of appetite. Severe epigastric pains, sometimes accompanied by 
vomiting, are not rare, and may continue for some time before the 
paralytic stage develops. 

The first manifest, and the most characteristic, symptom of coma 
is a sudden dyspneic frequency and depth of respiration ; at the 
same time the frequency of the pulse increases. Respiration fol¬ 
lows no distinct type,—especially not the Cheyne-Stokes,—inspira¬ 
tion taking place forcibly and deeply twenty or thirty times a 
minute in a blowing manner, even in cases in which postmortem 
examination subsequently shows a normal state of the lungs. The 
pulse runs up to from 130 to 1 50 or more, becomes extremely small, 
and can soon be no longer counted. The pupils may be strongly con¬ 
tracted. Mental excitation, often of great terror, may precede the 
depressing symptoms. Sometimes the dyspneic respiration and the 


* Diabetic coma was first described, in 1854, by v. Dusch, but it was little known in the 
profession until described twenty-one years later by Kussmaul. The majority of my 
diabetic patients in the severe stage have died in coma. Frerichs, among 250 patients, 
diabetic at the time of their death, found 150 cases of coma. A. James, of Edinburgh, 
however, encountered only 24 instances of coma among 50 fatal diabetic cases. In the 
other 26 cases death was due to pulmonary tuberculosis in 16 and to acute pneumonia or 
gangrene of the lungs in 8 cases. 



i3 2 


DIABETES MELLITUS AND GLYCOSURIA. 


quick, small pulse may continue for many hours, or even for days, 
before paralytic symptoms set in. Sometimes the first stage of ex¬ 
citation may pass so quickly and be so little marked, and the par¬ 
alytic stage set in so suddenly, that the condition can hardly be dis¬ 
tinguished from apoplexy or primary paralysis of the heart. Sooner 
or later the sensorium becomes clouded ; but even before this is 
manifest, the speech may denote incipient motor disturbance. The 
depression is generally supreme, signs of excitation being only 
slight and of short duration, and spasm being sometimes scarcely 
perceptible. The extremities become icy cold ; the temperature, 
which often before the attack was below the normal, now sinks still 
further. During this period the glucose, the urea, the toxic acids, 
and the other products of metabolism in the urine may be dimin¬ 
ished.* I may refer also to the small casts from the kidneys that 
Kiilz, among others, found to be numerous and constant (?) during 
coma. The comatose state may last for days, rarely for weeks, 
and sometimes only for hours. The average duration of life after 
the first manifest symptoms have appeared may be estimated at two 
or three days. Even if the patient, as sometimes happens, almost 
completely regains consciousness, and all symptoms of comatose 
depression recede, restitution to the preexisting state—though it is 
mentioned in literature by trustworthy observers—is extremely rare. 
When the nervous centers have once been attacked, all treatment, 
however energetic and quickly applied, almost always fails to bring 
about permanent recovery, and the physician does well not to let 
transitory improvement deceive him as to the approaching fatal 
issue. The last hours are generally quiet, with scarcely any other 
signs of life than the respiration and the pulse, and dilatation and 
contraction of the pupils, the latter often asynchronous. 

Diabetic coma is a state of poisoning—there is no doubt about that in the 
mind of any physician who has once seen it; but opinions as to the kind of 
poison differ greatly. At one time the hyperglycemia was suspected as a 
cause, but I consider this view to have only historic interest. The increased 
amount of sugar in the blood may reach higher figures in mild cases of diabetes 
with a free diet than in severe cases with restriction of the carbohydrates; but 
mild cases of diabetes— i. <?., cases in which glycosuria disappears when carbo- 


* Miinzer and Strasser, however, have found the nitrogen in the urine increased dur¬ 
ing coma; the excess may, however, have been produced before. 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 


133 


hydrates are excluded—do not develop coma. I consider that all reports of 
such an occurrence are the result of mistake, and represent cases of uremia or 
of primary heart-failure, etc. Complete exclusion of carbohydrates causes 
diminution in the hyperglycemia, but notoriously increases (the acidosis and) 
the danger of coma. Diabetic coma is sometimes not unlike uremia, from 
which it differs in several respects, and especially in the marked dyspneic 
respiration, though this may to some extent be present in the final stages of a 
number of different diseases. Besides, patients die in diabetic coma in the 
absence of serious changes in the kidneys. The Scotch theory as to fat- 
embolism in the brain has scarcely any basis at all, and has not survived. 
From 1857, when Petters, in a case of coma, found acetone in the blood and 
in the urine, the theory of acetonemia as the cause of diabetic coma was 
widely accepted ; but Kussmaul refutes this theory, and Frerichs, in the 
seventies, Albertoni, in 1884, and others proved that the toxicity of acetone, 
especially in view of the small quantity produced in diabetes, is insufficient to 
be considered a cause of death. Fer6, in fact, does not consider acetone much 
more poisonous than ethylic alcohol, which is drunk in such quantities by 
millions of human beings. 

Gerhardt, in 1865, discovered his most important reaction ; and when Deich- 
miiller, Tollens, and v. Jaksch had found it to be due to diacetic acid, suspicion 
fell on this substance; but here, again, the toxicity and the quantity were too 
small. When acetone and diacetic acid both pass over during distillation as 
acetone, scarcely ten grams of the latter can be obtained from the daily 
urine; and Brieger showed that injection into the blood of twenty grams of 
diacetic acid left the nervous system perfectly intact. 

Hallervorden had found the quantity of ammonia excreted in severe cases of 
diabetes enormously increased, and he and Coranda found that this increased 
ammonia corresponded to an increased excretion of acid. Walther, in 1877, 
showed that injection of acids into dogs produced a state quite similar to 
diabetic coma. On this basis Stadelmann, in 1883, made further investigations 
in cases of severe diabetes, and found what he first considered as a-crotonic 
acid, but what Minkowski and Kiilz later proved to be /Foxybutyric acid. 
Since Kiilz afterward found that the excretion of /Foxybutyric acid may amount 
to more than 200 (226.5) grams in twenty-four hours, this acid, not with¬ 
out good reason, has been considered to be the principal cause of diabetic 
coma, though the other acids (diacetic acid and fatty acids of low order), the 
acetone, and perhaps other still unknown toxins* may exercise a contributory 
influence. 

In this book I have adhered to the old division of diabetes into 
a mild and a severe stage, and this I believe to be the best and 
most practical, founded, as it is, on the absence or presence of gly¬ 
cosuria with abstinence from carbohydrates. Of late, however, 


* Ammonia may be present in increased quantity through the influences of other acids 
than /Foxybutyric acid (Rumpf, Strasser, and Miinzer). 





134 


DIABETES MELLITUS AND GLYCOSURIA. 


another classification has been made, namely, pancreatic , neurogenic , 
and constitutional diabetes. 

The pancreatic and the neurogenic varieties are considered, as a 
rule, to form together what I have called severe diabetes, character¬ 
ized by its sudden, comparatively acute appearance, its rapid de¬ 
velopment, the autophagy, the acidosis, and the frequency of death 
in diabetic coma. Pancreatic diabetes is distinguished from neuro¬ 
genic diabetes by (i) the absence of a nervous, etiologic factor; (2) 
the presence of local symptoms referable to the pancreas ; (3) pecu¬ 
liar qualities of the feces. 

The absence of a nervous etiologic factor only rarely helps in the 
differentiation, because almost all human beings have been subjected 
to such nervous influences as may cause diabetes, and because 
nothing is more common than an hereditary neurotic predisposition. 
In rare cases a tumor may be felt in the pancreas during life. 
Icterus also, when there are no other distinct causes for it, speaks 
for disease of the pancreas, which per se often causes icterus. Then 
there are sometimes colicky pains referable to the pancreas (not 
rarely accompanied by vomiting or by diarrhea) (Fleiner, Licht- 
heim, Naunyn). These pains may increase in severity for hours, 
are felt in the epigastrium, and radiate to the back. Sometimes 
they are observed in cases of calculi in the pancreatic ducts, and 
the stones, consisting chiefly of phosphates and calcium carbonate, 
may be passed with the stools (Minnich). Often, when the func¬ 
tions of the pancreas are impaired, the feces contain abnormal 
quantities of fat. Such stools, conspicuous by their light color, 
strongly suggest a pancreatic origin. Le Nobel also considers the 
absence of salts of the fatty acids simultaneously with the presence 
of large quantities of fat as characteristic of the feces in cases of 
pancreatic diabetes. As the pancreas is important in the assimila¬ 
tion both of proteids and of carbohydrates, the presence in the feces 
of abnormal quantities of undigested remains of both of these kinds 
of food also speaks for pancreatic diabetes. Finally, Le Nobel lays 
stress on the decrease in or absence from the feces and the urine 
of indol and skatol, and of the corresponding series of products of 
decomposition, with their combined sulphuric acid, in pancreatic 
diabetes. Naunyn, in his recent work, also mentions the late 
appearance in the urine, in cases of pancreatic diabetes, of the 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 135 

reaction for salicylic acid after administration of salol, which sub¬ 
stance, under the influence of the pancreatic juice, is quickly de¬ 
composed into salicylic acid and phenol. Otherwise the urine 
affords no information concerning the pancreas. The glycosuria, 
the phosphaturia, the azoturia, and the amounts in the urine 
of all products of metabolism are exactly the same in pancreatic 
as in other forms of diabetes. Von Ackeren’s and Le Nobel’s 
maltosuria seems to represent a mistake, as the sugar in the urine 
in dogs after extirpation of the pancreas is found to be glucose 
(v. Mering, Minkowski), and as many other pancreatic cases 
afterward observed constantly presented glucose in the urine. The 
liver, which Lancereaux first described as unduly large in neuro¬ 
genic, but as of normal size in pancreatic, diabetes, may, as he now 
acknowledges, be equally large in both conditions. It must further 
be remembered that symptoms referable to the pancreas need 
not be present in all cases of pancreatic diabetes. Neither need 
pancreatic or neurogenic diabetes always be the severe type ; it has 
been proved that severe lesions of the pancreas, as of the nervous 
system, may cause mild diabetes. In practice, many cases are en¬ 
countered in which it is quite impossible to decide between pan¬ 
creatic and neurogenic diabetes. 

Fully two hundred years elapsed between Brunner’s original 
attempt at extirpation of the pancreas (1686) and Minkowski’s and 
v. Mering’s discovery of the glycosuria resulting from that opera¬ 
tion. Yet Cowley, in 1788, noted atrophy of the pancreas due to 
concretions in a case of diabetes, and Haller observed intense 
hunger after extirpation of the pancreas. Within more recent 
times Bouchard, in 1851, expressed his opinion of a causal con¬ 
nection between diseases of the pancreas and diabetes, and Lance- 
reaux’s three cases (1877) established the matter in the mind of the 
profession. Later, N. Senn observed several symptoms of dia¬ 
betes in dogs after extirpation of the pancreas, and William T. 
Bull, after such an operation on a patient, observed diabetes. Both 
of these distinguished American surgeons, however, were con¬ 
cerned chiefly with the surgical features of their work, and they just 
missed adding a great discovery in experimental pathology to their 
other successes. The same fate befell Finkler and Orth, who had 
undertaken extirpation of the pancreas in dogs in order to observe 


I36 DIABETES MELLITUS AND GLYCOSURIA. 

any possible diabetic effect. They evidently failed in their purpose 
by not effecting complete extirpation.* Finally, v. Mering and 
Minkowski, in 1889, announced their great discovery at Strasburg. 
If we have been rather slow in acquiring facts, some of us, how¬ 
ever, are really much too quick in drawing conclusions, and there are 
some, especially in France, who consider that all cases of diabetes are 
of pancreatic origin, and who, as soon as glycosuria is mentioned, at 
once think of the pancreas, as quickly as they do of alcohol when 
delirium tremens is referred to. The clinician, however, who learns 
that a broker was attacked by diabetes after great losses, a statesman 
after a political failure, a woman after the loss of her husband, and 
any one after a severe blow on the neck, will scarcely believe that this 
effect has been brought about by the pancreas ; and when one finds 
postmortem that the pancreas, in fully nine out of ten cases, after 
diabetes is either normal, macroscopically and microscopically, or 
presents no greater change than a slight degree of atrophy, such as 
is found in many other organs, he does not gain the impression that 
the cause of diabetes is constantly to be found in the pancreas. 
Whatever information the future may bring, it is to-day absurd to 
insist upon a primary pancreatic cause for every case of diabetes, 
and facts rather point to the conclusion that pancreatic diabetes 
represents only a small minority of all cases of diabetes. 

Then there is the “ constitutional,” “ fat,” “ gouty,” or “ her¬ 
petic ” diabetes, which often seems to be a distinct type. These 
designations are used to indicate the mild cases with a course cov¬ 
ering many years, which develop slowly in middle age or in senility, 
and which often constitute rather a weakness than a disease. This 
condition is found almost exclusively among the upper classes, and 
usually among brain-workers. A diabetic of this kind generally 
has some hereditary neurotic, gouty, or adipose predisposition, 
which may have developed in several directions. He has usually 
been “ nervous ” throughout his whole life, and he has often suf¬ 
fered in youth from cutaneous eruptions (eczema, lichen, psoriasis). 
In middle-age he becomes sedentary, delights in the pleasures of 
the table (which often have to make up for a somewhat lowered 
virility), suffers from neuralgic, rheumatic, and gouty troubles, 


* Medical Congress at Wiesbaden, 1886. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 


137 


and begins to show glycosuria, which may amount to a mild dia¬ 
betes, with slight dystrophic troubles, cutaneous eruptions, fur¬ 
uncles, neuritis, brittle nails, defective teeth, etc. With many of 
these patients, especially those that suffer from gout, the chances 
of reaching advanced age are almost as good as with the average 
man, and their diabetes continues to be slight. An affection that 
begins as a “constitutional” diabetes may , however, in rare cases, 
later appear as a neurogenic one; neither is it perfectly certain that 
such an affection does not depend upon changes in the pancreas. 

It is impossible at present to decide what is hepatogenic diabetes; 
it is not even quite certain that this designation may not be applica¬ 
ble to all varieties of diabetes. In equal degree muscular diabetes 
is a mystery. Gastro-intestinal diabetes—with all respect to the 
honored name that first advocated this designation—according to 
all evidence does not exist at all. Re?ial diabetes is not deserving 
of the name diabetes, and has been mentioned among the glyco¬ 
surias. 


Bronze-colored Diabetes.* 

Since 1882, when a treatise by Hanot and Chauffard appeared,f 
about a dozen cases of a most peculiar form of diabetes have 
been described, almost all of which have occurred in France. 
This form of diabetes offers, clinically, a good deal of resem¬ 
blance to pancreatic diabetes, but it is apparently a disease sui 
generis , and is called “ le diabete bronzee,” from the color of the 
patient’s skin. Bronze-colored diabetes generally appears in men 
between forty and sixty years old; in most cases there has 
been a previous history of alcoholism or malaria. It presents the 
clinical picture of a severe diabetic syndrome, and is usually com¬ 
plicated with tuberculosis. In addition, there may be marked 
dyspeptic symptoms, considerable swelling of the abdomen, with a 
small amount of ascites, a hypertrophic, hard, and sensitive liver, 
some dilatation of the abdominal veins (rarely a distinct “ caput 


* “ La Cachexie Bronzee dans le Diabete,” Gonsalez Hernandez, Th£se, Mont¬ 
pellier, 1892. Pierre-Marie, “ Sem. Med.,” 1895. Brault and Gallard, Letulle, and 
others. 

t “ Revue de Med.” 

10 



I38 DIABETES MELLITUS AND GLYCOSURIA. 

Medusae ” around the umbilicus), high-colored urine, and pro¬ 
nounced cachexia. The most conspicuous symptom of all, how¬ 
ever, is a dark brownish-gray color of the whole skin, most pro¬ 
nounced in the face, on the extremities, and on the genitals. 

The disease invariably leads to death—usually in marasmus or 
coma—in about a year’s time. 

Besides the usual diabetic changes, almost all of the organs, but 
chiefly the liver, the pancreas, the walls of the alimentary canal, and 
the mesenteric glands, are found the seat of an abundant ocher- 
colored deposit, derived from the hemoglobin of the blood. This 
substance increases up to several thousand per cent, the amount of 
iron of the tissues (Hanot, Lapique, Parmentier and Carrion). 
(The same pigment is present in the malarial cachexia, in hyper¬ 
trophic cirrhosis of the liver, and in Addison’s disease.) The liver 
is found in a state of diffuse hypertrophic cirrhosis with pigmented 
cells. Its arteries are almost occluded as a result of endarteritis 
(Triboulet), and the portal system is remarkably dilated. Other 
organs also are often more or less cirrhotic. The red blood- 
corpuscles are diminished in number; Parmentier and Carrion 
found about 3,500,000 to the cubic millimeter. Several observers— 
e. g. y Anselme—consider the disintegration of the red blood- 
corpuscles from some unknown cause responsible for the diabetes 
by invading the pancreas and inducing cirrhosis. 

I have already mentioned that habitual excretion of glucose, 
however inconsiderable, generally becomes permanent, in so far that 
it occurs daily for some time after meals ; and that simple glyco¬ 
suria usually remains unchanged, though there are exceptions to this 
rule. 

In cases of true diabetes definitive cessation of glycosuria with a 
free diet is still rarer, and such complete and permanent restoration 
to health certainly does not occur in more than about one per cent, 
of all cases. I think it likely that this occurs chiefly in cases in 
which the diabetes has been caused by trauma or by infection, and 
that, when it takes place, the restoration is effected within a com¬ 
paratively short time. 

One often hears patients, and sometimes physicians, speak of 
recovery from diabetes and restoration to complete health. Almost 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 139 

all such reports will be found incorrect on careful investigation. 
Sometimes the glucose has disappeared with a restriction of carbo¬ 
hydrates and reappears with a free ordinary diet. In other cases 
transitory or periodic increase in the power of assimilation is re¬ 
sponsible for the mistake (see Periodic Diabetes). Other reports of 
like character refer to simple transitory glycosuria from some acci¬ 
dental cause, or even to the casual occurrence in the urine of 
reducing-substances other than glucose. 

I have, in practice, seen disappearance of glucose from the urine 
with a free diet only in three cases in which sugar had appeared * 
in diabetic quantities. In one of these cases there remained a dis¬ 
tinct polyuria,— i. e. } diabetes insipidus,—as has happened in several 
reported cases. 

My first case of recovery from diabetes was the one following 
influenza mentioned under glycosuria due to infection. Both the 
fully developed diabetes and the restoration of normal conditions 
for at least several months appear to me to be certain. 

The second case was that of a Scandinavian lady, fifty-one years 
old, who, after a violent blow on the forehead, felt exceedingly 
weak, and lost in weight for a considerable time. She did not 
remember any symptoms of diabetes other than pruritus vulvse. 
After a year and a half she at last consulted a physician, who found 
the urine to have a specific gravity of 1.037, and to contain a large 
amount of glucose; the presence of the latter was ascertained by a 
fully reliable investigation. When I saw the patient, half a year 
later, there was nothing noteworthy beyond some neurasthenic 
symptoms and a cataract in drop-form, which probably had nothing 
to do with diabetes. After five days of free diet with a consider¬ 
able amount of carbohydrate the urine did not contain glucose ; 
nor was there any pathologic trace of it in the urine collected for 
six hours after ingestion of 120 grams of glucose. Some time 
before this was written, three and a half years after her accident, 
the patient appeared to tell me of her complete recovery. She has 
observed no dietetic rules, but the urine has always been found free 
from sugar, and is so at present. 

* I have seen rather large quantities of glucose (for simple glycosuria) in typhoid 
fever disappear after the end of the fever, and I have seen diabetic quantities of glucose 
after influenza dwindle to simple glycosuria. 




140 


DIABETES MELLITUS AND GLYCOSURIA. 


The third case was Mr. F. D., a teacher from Boston, forty-five 
years old, who had, five months previously, without manifest cause, 
been seized with symptoms of diabetes ; a chemist of Harvard Uni¬ 
versity had found 7.5 per cent, of glucose in a specimen of his 
urine. The patient had for three months before arriving at Carls¬ 
bad observed a most rigorous diet. Under my care he gradually 
received an increased supply of carbohydrates, until more than two 
hundred grams a day were given. The urine, which contained no 
albumin, remained free from glucose during his four weeks’ stay in 
Carlsbad; but the quantity reached three liters a day, and the 
specific gravity was about 1.012. 

Thus, it sometimes, though rarely, happens that a true diabetic 
may be restored to health. Whether this ever happened in a case 
of severe diabetes is another matter ; so far as I know, not one cer¬ 
tain instance of this kind has been recorded. In my own experi¬ 
ence, I have never seen any case with diacetic acid (apart from 
inanition and in association with a full supply of food) in which this 
acid has disappeared.* 

Mild diabetes is compatible with long life, and I know of cases 
that in all probability have lasted forty years, and with certainty 
more than thirty years. A duration of twenty years is by no means 
rare. The outlook is the better, the later in life the disease sets in, 
the greater the power of assimilating carbohydrates, and the better 
the general somatic and mental state. A strong digestion is of very 
favorable moment. Trauma and infection as causes afford a better 
prognosis with regard to both complete recovery and a mild course. 
Gout and adiposity as complications are favorable signs, especially 
gout. Heredity does not seem to me so pernicious an influence as 
some authorities would make it. I have at least several times seen 
sons of diabetic fathers or mothers present through many years 
mild diabetes or simple glycosuria. Independent pecuniary re¬ 
sources and the ability to live without care in a suitable climate, 
and to afford a generous diet, are highly advantageous to the dia¬ 
betic patient. 


*Dr. Toepfer, of Carlsbad, has told me of such a case in a young diabetic girl, who 
one summer presented a distinct Gerhardt’s reaction, even while increasing in weight, 
and who the following summer exhibited no diaceturia. Such an occurrence is certainly 
exceedingly rare. 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 


141 


Mild diabetes more commonly remains mild diabetes than it 
develops into severe diabetes. On the other hand, a transition 
from the mild into the severe stage is no very rare occurrence, and 
it is difficult to understand how even specialists of wide experience 
can have failed to observe it. 

Severe diabetes rarely lasts more than four or five years ; the 
average duration can not be much above three years. In very 
severe cases, and especially in young persons (see below), the 
dystrophy may lead to death in a few weeks. 

I make the following twenty-four extracts from my records of diabetic 
patients. The cases are related as briefly as possible, and they are intended 
only to convey an impression of the general clinical picture of the diabetic 
syndrome and its common complications. The cases are arranged so as to 
represent different stages and to illustrate the gradual failure of the power of 
assimilation and the development of the glycosuric dystrophy. If one is 
anxious for appellations, he may call the first 8 cases simple glycosuria, the next 
8 cases mild diabetes, and the last 8 severe'diabetes, at the time when /^/in¬ 
vestigated. Matters of local significance, of nationality, of treatment, etc., are 
here omitted. The patients include Scandinavians, Americans, Germans, and 
Englishmen ; the first alone belonged to the Semitic race. 

1. Mr.-, thirty-two years old, came to Carlsbad with dyspeptic troubles, 

which showed themselves, however, to be only the gastric manifestations 
of a pronounced neurasthenia, partly inherited and partly acquired, chiefly 
through sexual excesses. The patient had of late years grown exceedingly 
“ nervous.” His restless sleep was of the usual neurasthenic type, with an in¬ 
terruption of complete wakefulness from 1 to 4 or 5 a. m. The man was 
irritable, often giddy, had a “ casque neurasthenique,” a beautifully pro¬ 
nounced “plaque sacree ” and other rhachialgic manifestations, shooting-pains 
in the legs after standing for some minutes, etc. The usual fear of suspected 
tabes was (as always) entirely unfounded ; thorough investigation demon¬ 
strated, even to the patient’s satisfaction, the absence of all symptoms of that 
disease, and, rather strangely, he had escaped syphilis. The man declared 
somewhat mournfully that coitus was no longer “what it had been, what it 
could be, and what it ought to be”; besides, the act had been of late suc¬ 
ceeded by a feeling of extreme weakness. 

The urine obtained one hour after the end of dinner constantly underwent 
reduction, which disappeared after fermentation. When reduction was most 
marked, the urine caused a slight deflection of the ray of polarized light to the 
right instead of the customary deflection to the left (from combined glycuronic 
acid). 

t 

2. Miss-, twenty years old, had been informed by her physician, eight 

years previously, that her urine contained sugar. There was no direct hereditary 




142 


DIABETES MELLITUS AND GLYCOSURIA. 


cause and no etiologic point other than some intellectual overwork and a dis¬ 
appointment in love just before the discovery of the glycosuria. 

At sixteen the patient had hysteric attacks and several stigmata. She was 
of a marked nervous temperament, and suffered still from periods of sleepless¬ 
ness, “ terreur nocturne,” and other manifestations of similar character. 
Sometimes during nervous exacerbations the patient herself was cognizant of 
polyuria and pollakiuria, with the almost colorless (“ spastic ”) urine secreted 
periodically by “ nervous ” persons. 

When the young woman consulted me she was at her best, and made the 
impression of a lively, fairly healthy individual, with no distinct hysteric* 
and only moderate neurasthenic symptoms, and presenting nothing remarka¬ 
ble apart from the urine, which repeatedly, in samples obtained an hour after 
meals, contained from 0.05 to 0.2 per cent, of glucose. On a perfectly free 
mixed diet the tall young woman passed 1850 cu. cm. of urine, with a specific 
gravity of 1.021 and a faint trace of glucose. Eight years after the discovery 
of the glycosuria I learn that the state has not changed, and that the general 
health is fairly good. 

3. Mr. J., fifty-nine years old, had a diabetic father, had himself worked 
hard intellectually for a large part of his life, felt a strong attraction to the fair 
sex, and thought American whisky a most delightful and wholesome bev¬ 
erage. He had been a hard smoker. The still deeply affected father was 
scarcely able to mention the terrible loss of a daughter two and a half years 
before. 

The patient came to Carlsbad for adiposity and gout (in the big toe !). Sleep 
was fairly good ; sexual power, considering age, likewise; and the knee-jerk 
present. The heart was somewhat weak, with distant sounds ; the organ was 
somewhat enlarged, the pulse small and weak, but fairly regular. The func¬ 
tions in general were tolerably well performed, and after a mild dietetic course 
and systematic exercises the patient took quite long walks in the hills around 
Carlsbad. The teeth were partly absent and partly affected with caries. 

On the back a gouty eczema existed. 

The ophthalmoscope disclosed a distinct picture of optic neuritis, chiefly 
marked on the right side (from tobacco and whisky). 

The patient assured me that his urine, recently analyzed, was normal. 
Finding him a sensible and not at all a hypochondriac person, I told him that, 
from his “tout ensemble,” I was quite certain that during some parts of the 
day it would contain small, clinically insignificant, but abnormal quantities 
of glucose—and a specimen obtained after dinner contained about 0.25 per 
cent. 

4. Dr. X, a physician, was descended from families both of which were free 
from developed psychoses, but which, together with some instances of great in¬ 
tellectual capacity, included others of “ eccentricity ” and extremely choleric 
temperament. 


* The field of vision was not examined. 




SYMPTOMS AND COMPLICATIONS OF DIABETES. 


143 


The patient himself was strong, but sensitive and lively as a child. He had 
suffered now and then from eczema, and had worked hard and participated a 
good deal in the customary dissipations at the university. At the age of twenty- 
three he was subjected to a powerful depressing emotion, and some weeks 
afterward a series of furuncles appeared. The patient at this time worked 
hard for academic honors, and a year later began to suffer from sleeplessness; 
diminution in sexual desire and other neurasthenic symptoms developed. At 
twenty-five the patient for the first time accidentally found a distinct trace of 
sugar in his urine ; this again happened when he had reached his thirty-second 
year. He then also found distinct oxaluria. Shortly afterward the patient, at 
a postmortem examination, contracted a severe pyemia, which wrecked him 
somatically and depressed him mentally for some time. At the age of thirty- 
eight the patient again accidentally found sugar in his urine, and in view of 
the two previous observations of the same kind, subjected himself to a thorough 
investigation. It was then found that a liberal supply of carbohydrates (sev¬ 
eral hundred grams) did not cause sufficient glycosuria to permit a distinct 
reaction with Nylander’s solution of the urine for the twenty-four hours, which 
amounted to between 1500 and 1800 cu. cm.; that the first specimen obtained 
an hour after dinner usually contained between 0.1 and 0.2 per cent, of glu¬ 
cose ; that the patient generally could take a large amount of rice or 300 grams 
of cane-sugar without the development of glycosuria; and that the slight amount 
of glucose that appeared in the urine after mixed meals with some wine could 
temporarily be increased quite considerably under the influence of emotional 
disturbances. On one occasion the patient, immediately after a rather sump¬ 
tuous dinner, was seized with an intense fit of anger ; a specimen of urine 
passed shortly afterward contained 1.4 percent, of glucose, the largest quantity 
observed among more than 100 analyses, of which only one other had yielded 
so much as 0.4 per cent. The patient now for three days lived chiefly on carbo¬ 
hydrates ; then collected the urine for twenty-four hours, and to his delight saw 
the phosphates form a beautifully white precipitate on boiling with Nylander’s 
solution. But few analyses have since been made, and these showed speci¬ 
mens of the urine collected for twenty-four hours to be practically free from 
glucose. The patient has presented gouty symptoms from his thirty-third year. 
The joints of the fingers from time to time suddenly swell and become tender. 
The great toe of the right foot also has been involved. Dr. X is now (1899) 
in his fifty-second year, and is rather healthier than twenty years ago. He is 
unwilling to permit further analysis, which formerly kept him in a hypochon¬ 
driac state. His weight keeps at the level of 95 kilograms. The patient was 
married eighteen years ago, and has six mostly strong and healthy children. 
One otherwise healthy child suffered for a long time from nocturnal enuresis 
and from psoriasis. 

Another physician, an apparently healthy, hard-working man, on hearing 
of Dr. X’s glycosuria, mentioned the fact that he had himself accidentally 
found sugar in his own urine sixteen years ago. An hour had just passed since 
his frugal dinner when this was mentioned. I expressed my opinion that the 
urine probably still contained glucose, and we found fully 0.2 per cent, of it in 
the specimen. 


144 


DIABETES MELLITUS AND GLYCOSURIA. 


5. An apothecary, forty-eight years old, whose father had suffered for 
many years in old age from diabetes, was terrified by finding sugar in his own 
urine. 

The patient presented the outward appearance of an unusually healthy, 
powerful man. During the preceding ten years his weight has kept at about 
107 kilograms, and his height was about six feet. Investigation failed to dis¬ 
close anything abnormal. Even most of the usual neurasthenic symptoms 
were absent, except a fear of approaching great depths and slight weakening of 
sexual power. 

The urine was collected several times for twenty-four hours, with an allow¬ 
ance of 120 grams of white bread and some green vegetables in the diet. The 
secretion varied from 870 to 1200 cu. cm. in amount, and from 1.033 t0 I *° 2 3 
in specific gravity. A specimen of the twenty-four hours’ urine contained 
scarcely so much as 0.05 per cent, of glucose. 

The patient took 300 grams of cane-sugar in one liter of Giesshiibler water, 
and after four and a half hours the urine was found free from glucose. The 
amount collected equaled 500 cu. cm., with a specific gravity of 1.016, and it 
contained about 0.05 per cent, of glucose. After being boiled with sulphuric 
acid the urine reduced as a solution of 0.24 per cent, of glucose. 

6. Mr. G. W., a bank clerk, fifty-six years old, was free from known 
hereditary predisposition or other etiologic influence worthy of mention other 
than a severe malaria thirty years before. He came to Carlsbad on account 
of constipation, which, together with flatulence, constitutes his chief complaint. 
He was a fat, exceedingly “nervous” man, with a melancholy, “fussy” tem¬ 
per ; had a pronounced “ casque neurasthenique ” ; slept badly ; did not like 
to go out on a balcony ; had weak sexual power; and was easily made tired by 
physical or intellectual exertions. 

I found glucose in the urine, which contained, besides, many crystals of 
calcium oxalate. The patient ate nearly 300 grams of bread a day, and what¬ 
ever he liked besides. A specimen of urine an hour after dinner contained 
1.1 per cent, of glucose ; but the mixed total quantity for twenty-four hours,— 
1500 cu. cm., with a specific gravity of 1.024,—not quite 0.1 per cent. 

The patient told me five years afterward (in Stockholm) that he went to 
Lindewiese, in Silesia, and lived exclusively on white bread, and that the 
sugar then disappeared from his urine. Investigation, however, proved the 
state to be exactly what it had been in Carlsbad. 

7. Mr.-, forty-six years old, a noted barrister, came to Carlsbad on ac¬ 

count of dyspeptic troubles and not excessive adiposity—he weighed 94 kilo¬ 
grams. The condition was much like that described in case 3. The patient 
had hereditary adipose and gouty tendencies ; had worked hard and smoked 
hard; had led a sedentary life and greatly enjoyed a good table. He was 
quite irritable, slept badly, and had incipient symptoms of smoker’s heart. 
I found 0.4 per cent, of glucose in a specimen of urine after dinner. Free 
diet is attended with the elimination of a normal quantity of a somewhat 
“ lithemic ” urine, containing a distinct trace of sugar. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. 


145 


Seven years afterward I saw the patient in his home. He was very active in 
his profession, had made a large fortune by speculation, and did not know 
anything about his glycosuria, suffering only from slight neurasthenic symp¬ 
toms. 

Nine years after our first acquaintance I again saw the patient. He had 
worked and speculated a great deal, had twice made and lost a large fortune, 
and had, still more than before, led a life of constant emotional activity. The 
former simple glycosuria now sometimes reached diabetic figures (two per 
cent.) in large specimens, and occasionally slight symptoms of diabetes mani¬ 
fested themselves. 

8. Professor-, fifty-eight years old, a distinguished surgeon, had had a 

rheumatic and gouty father, and had himself, eleven years before, discovered 
two per cent, of glucose in a specimen of his urine, having for some time pre¬ 
viously felt tired and worn out. 

A specimen of urine after a dinner with a moderate supply of carbohydrates 
had a specific gravity of 1.037, but was found (by titration and polarization) to 
contain only 0.25 per cent, of glucose. With a customary diet and some re¬ 
striction of carbohydrates the urine amounted only to somewhat more than a 
liter, with a specific gravity of 1.024 and somewhat more than 0.1 per cent, of 
glucose. 

The patient was slightly neurasthenic and distinctly “ lithemic.” Some 
trouble with the toes, especially the great toes, probably was of a gouty 
nature. 

9. Mr. E., judge, forty-seven years old, belonged to a family with strong 
neurotic tendencies, including several instances of diabetes. The patient had 
in his youth been addicted to masturbation, and several years afterward suf¬ 
fered from neurasthenia. Six years before coming under observation he had 
applied for life-insurance, but was refused on account of the presence of 
glucose in the urine. Shortly afterward he was seized with a violent attack of 
influenza, and during convalescence a specimen of urine obtained after dinner 
contained 3.2 per cent, of glucose. 

The patient was a heavily built man, who had recently, with rigorous dietetic 
restrictions, lost in weight. Finding that this regime affected his general 
health badly, he returned to a somewhat more liberal diet, with a moderate 
allowance of carbohydrates, felt considerably better, and regained his previous 
weight. There were no distinct diabetic symptoms except the glycosuria. Even 
the teeth were normal. There was a moderate degree of neurasthenia, with 
some disturbance of sleep, and other cerebrasthenic symptoms. The sexual 
power was somewhat impaired. There were five healthy children in the 
family. 

A perfectly free diet without any restriction whatever, and with quite a large 
quantity of carbohydrates, was attended with the secretion of 1300 cu. cm., 
with a specific gravity of 1.025 and 0.28 per cent, of glucose. A specimen 
obtained after dinner contained 1.34 per cent, of glucose. The patient was 
again put on a systematically but moderately restricted diet, and the urine con- 



146 


DIABETES MELLITUS AND GLYCOSURIA. 


tained only traces of glucose. Ten years after the discovery of the mild dia¬ 
betes I again met the patient and found the general state unchanged. 

10. Dr. H., a widely known physician, at the age of twenty-seven years acci¬ 
dentally discovered over two per cent, of glucose in a specimen of his urine. 
There was no hereditary influence, but a history of much intellectual effort. Nor 
were there other symptoms of diabetes. The quantity of urine had always 
been rather large, though it had never amounted to distinct polyuria. The 
patient kept himself under some dietetic restriction, and the glycosuria disap¬ 
peared for several years and did not reappear even upon a free diet. Six years 
after its first discovery the glycosuria again appeared, following an attack of 
typhoid fever, and sometimes reaching considerable proportions. 

Fourteen years have now elapsed since the sugar first appeared in the urine. 
The patient, a man of iron will, adheres constantly to a diet with an allow¬ 
ance of about seventy grams of carbohydrate a day, and is free from deter¬ 
minable glycosuria. When for experimental purposes a greater allowance is 
made, the sugar again appears in moderate but quite determinable quantities. 
This most valued friend of mine, who is a hard worker, suffers from no other 
symptom than periodic insomnia. 

11. Lieutenant-Colonel R., a retired officer, eighty-one years old, has no 
knowledge of hereditary or other morbid predisposition. Thirty-nine years 
before coming under observation the man suddenly had a succession of fur¬ 
uncles, and he dates his diabetes from this time; the glycosuria, however, was 
not discovered until sixteen years later. 

The patient, who has been under my care for many years, is at the present 
time (1899) a lively old gentleman, with a healthy appearance. Only during 
the last two years has he observed any failure of memory ; he has also pru¬ 
dently left off playing whist, in which pastime he was, up to his eightieth year, 
considered to have few equals. The patient suffers from insomnia. Some¬ 
times there is giddiness. The reflexes, especially the knee-jerks, are weakened. 
Most of the teeth are absent, but the cavity of the mouth is otherwise normal. 
There is no odor of acetone from the breath. The patient is presbyopic, but 
the visual acuity is fairly good. Gerontoxon is not very strongly developed. 
There is some slight rigidity of the radial and temporal arteries. 

When the patient partakes of a moderate but undetermined quantity of 
bread and green vegetables, he passes about two liters of urine containing 
about two per cent, of glucose or a little more. There is no albuminuria. 
One hundred grams of Graham bread (about forty grams of carbohydrate) and 
some green vegetables yield 1750 cu. cm. of urine, with a specific gravity of 
1.025 and containing 0.8 per cent, of glucose. 

The patient’s wife also suffers from mild diabetes. 

12. Baron X, fifty-eight years old, a statesman, had a gouty inheritance; 
his mother also probably suffered for many years from diabetes. The patient 
has for forty years been a heavy smoker, and had been much interested in his 
good table. His restless spirit, quarrelsome temper, and heavy responsibilities 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


147 


had caused him a life full of emotions. In early manhood he suddenly in¬ 
creased considerably in weight. Twenty-six years before coming under obser¬ 
vation he had several furuncles. Already at this period his teeth began to show 
caries, and they successively fell out; the patient had often suffered from gin¬ 
givitis. The last molar tooth was sneezed out two years before my first inves¬ 
tigation. The glycosuria, which in small specimens of urine has reached over 
six per cent., was discovered only a year before the patient came to me. There 
was no albuminuria and no diaceturia. 

The patient had a weak nervous system, and periodically suffered from vio¬ 
lent supraorbital neuralgia. Some years previously he was troubled with 
agoraphobia ; he always carefully shunned steep declivities. Creeping sensa¬ 
tions in the legs and nocturnal cramps in the calves caused annoyance. 
There was no distinct neuritis. The left knee-jerk was weakened. 

The spleen was somewhat enlarged (the patient had had malaria eleven 
years before). The liver appeared of normal size on percussion and palpation. 
The heart was somewhat large and not powerful. 

During two seasons in Carlsbad I found that the patient, who was a little 
less unreliable during his “cure” than at home, when taking 120 grams of 
white bread and some green vegetables with his food, presented a gradual 
diminution in his glycosuria, until in the third week he was passing about 1800 
cu. cm. of urine containing only a trace of sugar. 


13. Herr S., forty years old, an engineer, had some months previously 
suffered from a remarkably obstinate ulcer on his leg, and his physician found 
six per cent, of glucose in the urine. 

The patient was free from neurotic or diabetic inheritance. He had rarely 
neglected free libations of strong grog in the evening and had smoked im¬ 
moderately. During the preceding few years he had suffered from gouty 
troubles. Four years before he had passed through a violent attack of influ¬ 
enza. The patient denied syphilis, but his wife had twice miscarried in the 
sixth month. 

The patient is a robust man, without obvious manifestations of theglycosuric 
dystrophy. Even the cavity of the mouth exhibited nothing abnormal beyond 
caries of two teeth. Sexual power was rather weak. The knee-jerks were 
just perceptible. The patient now and then felt pain “ deep in the head.” 

His heart was somewhat enlarged, the sounds weak and distant, the impulse 
not perceptible; the pulse 76, not quite regular, and weak. The temporal 
arteries were unduly distinct on palpation. 

One hundred grams of white bread and some green vegetables with the 
food yielded regularly about 2100 cu. cm. of urine, with a specific gravity of 
1.027 and containing 0.9 per cent, of glucose, a trace of albumin, and some 
granulated tube-casts. After two days of abstinence from carbohydrates the 
patient was able to take regularly sixty grams of white bread a day with green 
vegetables, without any determinable glycosuria. 

Nearly three years after this the patient again consulted me. He had, two 
weeks before, while driving about in a cab, suddenly lost first his sight and 
shortly afterward consciousness, having previously suffered from acute, deep- 


148 


DIABETES MELLITUS AND GLYCOSURIA. 


seated pains in his head. Consciousness returned after some hours. There 
were no distinct paretic symptoms, but amblyopia persisted for several weeks. 
The patient could at first only count fingers, but not read. Vision gradually 
returned to the previous state. The patient’s physician believes the symptoms 
to have been due to uremia, while I attribute them to cerebral hemorrhage. 
The ophthalmoscope disclosed a hemorrhagic retinitis, with ecchymoses in dif¬ 
ferent stages. The glycosuria was now, probably in consequence of the cirrho¬ 
sis of the kidneys, slighter than it had been three years before ; 120 grams of 
white bread and some green vegetables causing only faint traces of glucose to 
appear in the urine, of which about two liters were excreted in the twenty-four 
hours, and which had a specific gravity of 1.021 and contained a trace of 
albumin. 

14. A., a restaurateur, forty-seven years old, developed three “ maux per- 
forants ” on the right foot, and consulted Dr. H. Toll, who found a large 
quantity of glucose in the urine and called me in consultation. The patient 
admitted having “ wet his tongue nowand then,” which means in Sweden 
that he has drunk enormously. 

The man was somewhat maudlin, slept badly, presented no knee-jerks, 
had weakened sexual power, and complained of right genitocrural neuralgia. 
The pupils differed distinctly in size. The patient denied all history of syphilis. 
His heart was somewhat large, his pulse small and weak, but regular. Pro¬ 
nounced arteriosclerosis was obvious in the radial, temporal, and femoral 
arteries. There were no appreciable signs of cirrhosis of the liver. 

Restriction of the diet caused disappearance of the glycosuria and of the 
distinct polyuria, and the patient excreted in twenty-four hours 1500 cu. cm. 
of urine of a specific gravity of 1.035 an d, rather remarkably, free from al¬ 
bumin. 

The three “ maux perforants ” had made terrible ravages in the foot, which 
was already resected through Chopart’s joint; the process now continued 
chiefly along the tendons of the peroneal muscles. Sensibility was distinctly 
diminished on this leg, and there was a distinct retardation of the perception 
of needle-puncture. There being no indication of a clot in the popliteal artery, 
I proposed amputation below the knee, which was effected, with an excellent 
result after a few weeks of dietetic and restorative treatment. Nearly three 
years later I learned that the patient was still alive and in possession of a 
good stump. 

15. E., fifty-four years old, manager of a factory, ten years ago sought 
life-insurance, but was not accepted on account of the existence of glyco¬ 
suria. The history gave no clue to the origin of the diabetes. 

The patient one night awoke with an attack of serious indisposition, felt a 
sensation of pressure or weight in the occiput, and vomited profusely. The 
next day the lower branch of the facial and the abducens nerve on the right 
side were paralyzed. The patient now consulted Dr. Nordenson, who made 
the following note : “ In both eyes numerous small hemorrhages in the retina ; 
around the macula lutea round whitish patches, with small points of blood. 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


149 


Field of vision, normal extent; normal color-perception. Left eye: hyperme- 
tropia, 1 D.; visual power, 0.3. Right eye: hypermetropia, 1.50 D. ; visual 
power, 0.3. 

Seven weeks later the patient came to Carlsbad. I then found the lower 
branch of the right facial nerve and both abducens nerves paralyzed—the 
right eye alone seemed to be used. Other symptoms referable to the nervous 
system, besides the usual neurasthenic symptoms, included a feeling of heavi¬ 
ness in the occiput and some giddiness. The knee-jerk was absent on the 
left and barely appreciable on the right. A large specimen of the urine con¬ 
tained about three per cent, of glucose, but no albumin and no diacetic acid. 
Eighty grams of Graham bread and some green vegetables a day yielded a 
urinary secretion of from 2700 to 3000 cu. cm. a day, and, quite constantly, 
about 26 grams of glucose. A strict diet would, beyond a doubt, have caused 
entire disappearance of the glucose. With the use of syzygium jambolanum 
on three different occasions the glycosuria, ceteris paribus , sank to 15 grams, 
without any other appreciable change. In the autumn the neuroparalytic 
symptoms had disappeared, but otherwise the state of the eyes had undergone 
no change. 

A few months after his visit to Carlsbad I was called early one morning to 
the patient in Stockholm. He had again had at night a cerebral attack like 
the previous one. After a rectal injection, application of an ice-bag to the 
occiput and of hot bags to the feet, and elevation of the head, the attack was 
soon over without leaving any noteworthy sequel. 

Half a year later gangrene made its appearance in the left leg, and while 
the patient was under treatment for this a renewed cerebral attack suddenly 
ended his life. I was not at hand and there was, unfortunately, no postmortem 
examination. 

16. E. T. B., a farmer, seventy-two years old, was considered by his family 
and friends to be a healthy and active old man. Apart from his eyes he had 
suffered from no disease whatever, and he knew of no reason for believing 
that any existed. He himself and others, however, were struck by a “ pecu¬ 
liarity ” that had made its appearance about thirty years previously—namely, 
that he drank more water and passed a greater quantity of urine than other 
persons. 

The patient complained that his eyes had for many years been a source of 
trouble, and stated that he had used only the left one. Some days before 
coming under observation this eye began to ache; the patient obtained from a 
neighboring physician some atropin, which made the eye ache “ horribly.” 
He then consulted Dr. Nordenson, who found the cause of the “ peculiarity,” 
and sent the patient to me on account of his diabetes. 

The right eye presented an absolute glaucoma. The upper lid was some¬ 
what swollen, the conjunctiva of the bulb was hyperemic, and there was 
marked pericorneal injection. The cornea was smoky, the pupil dilated, and 
the anterior chamber was wanting. The vitreous body yielded a yellowish- 
brown reflection (hemorrhage). 

In the left eye there was found hypermetropia of 1.50 D, with a visual acuity 


DIABETES MELLITUS AND GLYCOSURIA. 


150 

of 0.8 ; except for a pronounced gerontoxon, the cornea was normal. The iris 
also was normal and reacted well. At the bottom of the eye small yellowish 
patches could be seen between the inferior temporal and the inferior nasal 
vein. A considerable hemorrhage and some small ecchymoses were visible. 

The patient did not complain of any nervous disorder ; the sensibility in the 
left leg, however, was much impaired. The knee-jerk in the same side was 
almost destroyed; the toe-nails were discolored, strongly curved, thick and 
brittle ; on the plantar aspect of the great toe, beneath the interphalangeal joint, 
there was a circular scar attached to the bone and evidently from a “ mal 
perforant,” which had healed a couple of months before, under treatment by a 
surgeon, who, by the way, seemed to have omitted to look for diabetes.' 

On the right leg there was no “ mal perforant,” and the nervous and dys¬ 
trophic changes were much less marked than on the left leg.* 

The temporal and radial arteries were somewhat rigid, pulse 104, at noon, 
before lunch. The amount of urine secreted with free diet was 2.5 liters, with 
a specific gravity of 1.046, and it contained eight per cent, of glucose. 

A diet including an abundance of green vegetables, about 100 grams of pota¬ 
toes, and 100 grams of rye-bread yielded 1600 cu. cm. of urine containing five 
per cent, of glucose, but no diacetic acid. It is probable that with a strict diet 
the urine would have been free fronrglucose. 

Three years later the patient was said to have been in about the same 
state. 

17. A judge, sixty-one years old, nine years before coming under observa¬ 
tion, after some loss of weight and a sense of weakness, was discovered to be 
diabetic. The patient himself believed the dystrophy to be due to exposure to 
cold, and no other cause, hereditary or acquired, could be elicited. During 
his first season at Carlsbad the patient felt fairly well, and the neurasthenic 
symptoms, which constituted his chief complaint, subsided with the complete 
rest of his sojourn at the spa. 

The power of assimilation was quite good, and with a daily allowance of 
some green vegetables and 150 grams of Graham bread, the patient passed 
1600 cu. cm. of urine, with a specific gravity of 1.025, and containing only faint 
traces of glucose. 

Two years later the patient looked much less well and complained of in¬ 
creasing weakness and incapability of fulfilling his public duties. Investiga¬ 
tion shows, apart from the results of urine analysis, only one important change 
from the state of two years before—namely, there was now a distinct odor of 
acetone on the breath. The glycosuric dystrophy had made considerable prog¬ 
ress, and 75 grams of Graham bread and some green vegetables yielded 1800 
cu. cm. of urine containing 1.3 per cent, of glucose. There was then no dis¬ 
tinct Gerhardt’s reaction. The patient, who seemed entirely reliable, was fora 


* About the same time Dr. Kinnicutt, of New York, to whom I mentioned my case, 
had a similar one under observation, with marked neuritis, knee-jerk almost destroyed, 
“mal perforant,” and other dystrophic changes in the one leg, with a comparatively 
normal state in the other. 



SYMPTOMS AND COMPLICATIONS OF DIABETES. I 5 I 

whole week put on strict diet, with exclusion of carbohydrates. He then lost 
weight from 95.3 kilograms to 93.4 kilograms, and the urine yielded a faint 
Gerhardt’s reaction indicative of the presence of diacetic acid. There was even 
now about 0.1 per cent, of glucose in the urine ; this could scarcely have been 
derived from carbohydrates, but it seemed to be derived partly from albumin. 
The patient undoubtedly has arrived at the boundary line between the posi¬ 
tively mild and the positively severe stage, but his exact place can not be deter¬ 
mined under the conditions that prevail at Carlsbad. 

Four years later I learned that the man was still alive. 

18. A merchant first became my patient in his thirty-sixth year. His father 
had been diabetic, and a paternal uncle diabetic and insane. Seven years 
previously the patient contracted syphilis, and he had always been a hard 
drinker. Half a year before coming under observation the patient observed 
that white spots were left by his urine, which was found to contain six per cent, 
of glucose after dinner. Beyond this and moderate neurasthenia the man was, 
during his first season in Carlsbad, fairly healthy and quite robust-looking. 
Thirty grams of bread and some green vegetables were permitted with the 
food, without the development of glycosuria. As the patient with this restric¬ 
tion maintained his weight (92 kilograms) the diet was continued for five 
weeks. 

In the following summer the condition of affairs appeared pretty much the 
same. Sixty grams of bread and some green vegetables caused a trace of glu¬ 
cose to appear in the urine; the bread being increased to 90 grams, the nor¬ 
mal quantity of urine for twenty-four hours contained fully 0.1 per cent, of 
glucose. The patient had entered into matrimonial plans, and combated ener¬ 
getically my somewhat feeble opposition, asserting that Providence itself was 
strongly interested, but promised moderation in all respects. 

Two years later the man again appeared in Carlsbad, having carried out 
his plan of marrying, but having entirely forgotten his promise of moderation. 
Sixty grams of bread and some green vegetables now yielded 1450 cu. cm. of 
urine in twenty-four hours, with a specific gravity of 1.032 and containing 0.2 
per cent, of glucose and no diacetic acid. When carbohydrates were entirely 
excluded for some days the patient lost somewhat in weight, while the glucose 
entirely disappeared, and a faint Gerhardt’s reaction developed with ferrichlo- 
rid. As the drops of the solution fell in the urine they were, for a moment, 
surrounded by a purple zone, the urine above the phosphates having the 
color of sherry. In the following year the power of assimilation had 
again decreased, and the patient was in the severe stage of the dystrophy. 
Abstinence from carbohydrates was no longer followed by disappearance of 
the glycosuria, though only a few grams of sugar were excreted during the 
twenty-four hours. Gerhardt’s reaction was now well pronounced. About 
70 grams of bread and some vegetables yielded 1500 cu. cm. of urine, with a 
specific gravity of 1.034 and containing rather more than one per cent, of glu¬ 
cose. Upon this diet the patient kept his weight, but a distinct though faint 
Gerhardt’s reaction could still be elicited. 

Two years again passed and the patient returned to Carlsbad. The bodily 


152 


DIABETES MELLITUS AND GLYCOSURIA. 


weight was almost the same ; the glycosuric dystrophy had again made some 
slight progress. Mentally the patient was an altered man. He suffered from 
melancholia, without stupor or hallucinations, but with unfounded ideas of 
financial ruin, many expressions of “ tedium vitae ” ; terrible anxiety for the 
future mental and somatic fate of a new-born son, great restlessness, with an 
occasional “ raptus ” during the nights, and general profound depression, etc. 

The “ cure ” at Carlsbad somewhat improved the man’s condition; but 
during the autumn the melancholia again regained its sway over the patient, 
who, some months after my losing sight of him, was found lying across a rail¬ 
way track dead and mutilated. 

19. H., a clerk, forty-six years old when I saw him for the first time at 
Carlsbad, had known for two years that he was diabetic, but distinct polydipsia 
and polyuria had been present for five years. 

A history was obtained only with the greatest difficulty, owing to the stu¬ 
pidity of the patient, who did not seem to know anything of his whole past 
life, except that he had acquired syphilis twenty-nine years before and had 
successively passed through five antisyphilitic cures. 

The man was extremely peevish and irritable; he slept badly. Sexual 
power was enfeebled. Supraorbital neuralgia was present on both sides. The 
teeth were partly carious and partly gone. 

The urine, which had lately contained so much as seven per cent, of glu¬ 
cose, was now found to contain three per cent. There was no odor of acetone 
on the breath, no diaceturia, no albuminuria. A restricted diet put an end to 
the glycosuria, which afterward did not return in determinable quantities so 
long as the patient took no more than 60 grams of white bread and some green 
vegetables. 

Ten years afterward the man returned to Carlsbad. His breath now dis¬ 
tinctly smelled of acetone ; the teeth were almost all gone ; the tongue showed 
longitudinal and transverse furrows “ala crocodile .” Sexual potency was 
entirely gone. There was a suspicion of neuritis in both legs. The apex of 
the right lung exhibited signs of tuberculosis, and in one place there was a 
small cavity. The pulse was 84, the temperature slightly elevated. The 
patient complained of night-sweats. 

Exclusion of carbohydrates for several days reduced the glycosuria to 0.6 
per cent., 1500 cu. cm. of urine with a specific gravity of 1.026 being secreted 
in twenty-four hours; and a distinct Gerhardt’s reaction was present. Eighty 
grams of bread and 100 grams of levulose and some green vegetables with the 
food considerably increased the glycosuria, but distinctly diminished the diacet¬ 
uria (which, however, still continued), caused some restoration of weight pre¬ 
viously lost, and maintained the bodily weight at 77 kilograms. Syzygium 
jambulanum, even in large doses, had no appreciable effect. 

20. Mrs. L., thirty-eight years old, knew of no hereditary or other etiologic 
causes for her condition than an excessive fondness for sweets. Her diabetes, 
to judge from the polyuria and the polydipsia, had probably set in two years 
before. The patient was extremely stout, and did not lose in weight until her 
diet was restricted. 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


153 


During her first season in Carlsbad the lady appeared in fairly good general 
health. There was no smell of acetone on the breath. Some teeth were carious, 
and now and then gingivitic troubles arose. Some of the usual neurasthenic 
symptoms were present, and on the left side supraorbital neuralgia and sciatica. 
Cramp occurred at night in the calves of the legs. There was a tendency to 
profuse perspiration. Finally, the patient complained of pruritus vulvse, which 
speedily ceased on application of a solution of mercuric chlorid(i : 1000) twice 
a day. The urine, which had contained four per cent, of glucose, became 
normal in quantity and quality upon a restricted diet, and remained so, except 
for small traces of sugar excreted, when 60 grams of white bread and some 
vegetables were added to the dietary. 

Eleven years after the beginning of the diabetes the patient again appeared 
in Carlsbad in a very different state. She had diminished in weight from 86 
to 67.15 kilograms and she felt very weak. The skin was dry and of cyanotic 
hue upon the cheeks. The patient was no longer troubled with profuse perspira¬ 
tion. The breath smelled of acetone ; the teeth were defective ; the tongue was 
dry, partly coated, and of an angry red at the apex. Restriction of diet no 
longer stopped the glycosuria. The weight could not be maintained with less 
than 100 grams of Graham bread and some vegetables with the food, upon 
which the patient passed 2500 cu. cm. of urine containing 2 per cent, of sugar 
and with a distinct (but not marked) Gerhardt’s reaction, but no albumin. 

A year later small ecchymoses or petechiae, sometimes observed in advanced 
cases, began to appear. The petechiae disappeared when the patient remained 
in bed, and reappeared as soon as she moved about. They were present 
almost exclusively on the legs, only a few being visible on the trunk and none 
on the arms. 

Another year added iritis on both sides and cyclitis on the left side to the 
other symptoms. The patient was then in an advanced cachectic state, and 
died in coma a few weeks after the appearance of the ocular symptoms. 

21. Captain-, forty-four years old, an officer of the Guards, had in the 

spring received from his physician the information that he was diabetic, and in 
August he came to Carlsbad. 

The patient had during the preceding months at home felt some increased 
thirst and some need of passing his urine more frequently than before; still, 
the quantity did not distinctly exceed the normal limits. Apart from the urine— 
which at the time of the patient’s arrival contained a considerable quantity of 
glucose—there were scarcely any symptoms at all. All carbohydrates were 
excluded from the food, and during a week of strict diet the patient’s weight 
went down from 86.7 kilograms to 85.3 kilograms. The man now gradu¬ 
ally received increased amounts of carbohydrate. The urine remained nor¬ 
mal in quantity and quality until more than 90 grams of Graham bread and 
some vegetables were given. The patient had a splendid appetite, and one 
day passed 18 grams of nitrogen with his urine. When 120 grams of Graham 
bread were given, the mixed urine for twenty-four hours contained fully 0.1 
per cent, of glucose. The patient maintained his weight and felt as well as 
ever. 


% 


11 



154 


DIABETES MELLITUS AND GLYCOSURIA. 


The next year the man again appeared at Carlsbad, on May 7th. His gen¬ 
eral appearance had undergone a change for the worse, and there was an omi¬ 
nous smell of acetone on his breath. The bodily weight had fallen to 83 kilo¬ 
grams. The urine contained much glucose, and yielded a distinct though not 
very marked Gerhardt’s reaction. After an exclusion for five days of carbo¬ 
hydrates the patient passed 2200 cu. cm. of urine, of a specific gravity of 1.018, 
with 0.5 per cent, of glucose, and yielding a somewhat more pronounced reac¬ 
tion with the solution of ferric chlorid than at the patient’s arrival. The 
patient now received, daily, a large piece of Seegen’s almond-bread, which, as 
it is sold in Carlsbad, contains a not inconsiderable quantity of starch, and a 
generous supply of fish, meat, butter, and eggs. He then excreted 19.5 grams 
of glucose daily and Gerhardt’s reaction was less pronounced, though distinct. 
He still lost in weight, and added to his bill of fare 100 grams of levulose 
daily. The glucose in the urine increased from 19.5 to 34 grams in the 
twenty-four hours, but the diaceturia evidently decreased and the patient 
maintained his weight, which now was only 82.4 kilograms. Some ordinary 
bread was now given, and the bodily weight rose to 83.3, which it still was 
when patient left for home, after a stay of five weeks. There had constantly 
been some diaceturia. 

The patient, whom I asked concerning the presence of fat in the feces, 
was able to detect no difference from the ordinary appearance. 

On October 17th, while upon a fair amount of carbohydrates allowed by his 
physician at home, the man expired in diabetic coma. No autopsy was per¬ 
formed. 

This case represents the most rapid transition from a distinctly mild to a 
distinctly severe diabetes that I have ever witnessed. 

22. V. X., thirty-five years old, a diplomatist, belonged to a family that has 
given me diabetic, fatty, and gouty patients. The man had been a hard 
smoker. In the course of a diplomatic mission to Asia he had to stand a good 
deal of fatigue and of emotion. In the south of Europe he contracted malaria. 
A few months afterward diabetes suddenly set in, and took the patient to 
Carlsbad during three successive seasons. 

The man was exceedingly sensitive in every respect, slept badly, and a 
steep declivity made him giddy. The knee-jerks were present and moder¬ 
ately strong. The sexual power was somewhat weak, although the patient 
begot a child about two years after the beginning of his disease. The bodily 
weight had lately kept at about 73 kilograms. A few days after our first 
acquaintance he invited me to breakfast, where he consumed a piece of 
Graham bread, a large piece of butter and another of cheese, one partridge, 
two sausages, a considerable quantity of ham, and four eggs. We often after¬ 
ward took meals together, and I always found him with an enormous appe¬ 
tite. 

The teeth grew more and more carious, and the tongue showed more and 
more of the customary appearance in severe diabetes. The pulse was rarely 
below 100. The skin was dry and the patient was often troubled by itching. 

The urine after a few days’ absolute diet contained between 1.4 and 1.6 per 


SYMPTOMS AND COMPLICATIONS OF DIABETES. 


155 


cent, of glucose in about three liters. With the moderate quantity of carbohy¬ 
drate necessary for the maintenance of the bodily weight and of a fairly good 
general condition it increased to about four liters, containing between 2.6 and 
3 per cent, of glucose. During the whole time Gerhardt’s reaction was quite 
distinct, and the urine was repeatedly found to contain some /3-oxybutyric 
acid. A trace of albumin was always present. 

When the patient arrived at Carlsbad for the third time there was no oppor¬ 
tunity to analyze the urine. He was then in a state of utter exhaustion ; the 
frequent pulse and the dyspneic respiration already foreboded coma, although 
they were to some extent affected by a left-sided pneumonia. The patient 
was seized with a chill on the cars. A flat sound on percussion was elicited 
over the lower part of the upper lobe of the left lung, and in the same area 
distinct, though distant, bronchial respiration was audible. Constipation had 
been present for fQur days. 

A large, tepid, rectal injection, with the addition of potassium permanganate, 
whisky and enormous doses of sodium bicarbonate by the mouth, were imme¬ 
diately given. Coma gradually overwhelmed the patient, the specific gravity 
of the urine, which from the beginning of his disease had always been above 
1.035, falling to 1.019, and the glucose to 1.3. Gerhardt’s reaction, which had 
been very pronounced, became much less so ; still, there seemed to remain some 
/?-oxybutyric acid to the end. There was some expectoration of pneumonic 
sputa. Death took place six days after the patient’s arrival. 

On postmortem examination a central, small pneumonia was found in the 
left lung. The pancreas was perhaps somewhat too soft in consistency and 
undersized ; otherwise it was normal. The liver was in a state of pronounced 
fatty degeneration. The spleen was hyperemic and about twice the normal 
size. The kidneys were large, hyperemic, with the cortex slightly discolored 
by fatty degeneration. 

23. Miss B., a teacher of music, after a severe attack of influenza was seized 
with severe diabetes. 

Her general health failed rapidly, and she lost quickly in weight, in spite 
of an enormous appetite. She passed daily about four liters of urine. 

One year and a half after the beginning of the glycosuric dystrophy she 
came to Carlsbad in a most miserable cachectic and marantic condition. 
Eighty grams of Graham bread and some vegetables in the food yielded 2009 
cu. cm. of urine, with a specific gravity of 1.037, containing 4.4 per cent, of 
glucose and yielding a strongly marked Gerhardt’s reaction. The day before 
coma set in I took a specimen of the urine and found, after thorough fermenta¬ 
tion and precipitation with ammonia and lead acetate, the ray of polarized light 
deflected to the left between 0.4 and 0.5 0 in Hoppe-Seyler’s instrument. 

During her three weeks’ stay at Carlsbad a most wonderful contrast was 
evident between her miserable somatic and her splendid mental state; her 
courage not only keeping her in a happy frame of mind, but enabling her con¬ 
stantly and patiently to cheer another (most intractable) diabetic lady. I had 
not omitted to warn her of the danger of any continued constipation ; never¬ 
theless she remained in such a state for four days without taking the prescribed 


156 


DIABETES MELLITUS AND GLYCOSURIA. 


measures. She then, during a walk in the woods, was seized with the pro¬ 
dromes of coma, and was brought back to her hotel, where I immediately 
arrived. The brave little patient presented a pulse of 120 and the ominous 
“ blowing ” respiration. An immediate purging injection was given ; she 
besides received whisky, enormous doses of sodium bicarbonate in Geisshlibler 
water, and general massage. Being able to take no solid food, the patient 
drank a good deal of levulose in Geisshlibler water. After a distinct but trans¬ 
itory improvement the coma gradually overpowered the patient, and after 
more vigorous clonic convulsions than I ever saw before with this kind of 
death, the girl succumbed on the third day. 

24. Augusta J., forty years old, a widow who had married again, grieved 
greatly at the drunkenness and general moral degeneracy of her second hus¬ 
band, a laborer, and was suddenly seized with symptoms of diabetes. On 
October 29, 1891, about a year after the beginning of her diabetes, the woman 
entered Queen Sophia’s Hospital, in Stockholm, to be operated on for cata¬ 
ract by Dr. Nordenson, who, previously to the operation, confided her to my 
care for her diabetes. 

The patient was very thin, with a dry, scaly skin. Her tongue was thickly 
coated at its base, and presented the customary diabetic type, “ a la peau croco¬ 
dile ,” with some fleshy-looking patches and an atrophic mucous membrane. 
The teeth were carious and the breath smelled of acetone. 

The patient suffered from continuous headache and slept badly. There was 
no knee-jerk. Hearing was poor; vision, which was excellent a year before, 
was destroyed by the soft, diabetic cataract. At the apex of the right lung there 
was in a small area a somewhat sharp respiratory sound and a higher-pitched 
percussion-note. The pulse was 100. 

The headache might have been a precursory sign of coma; but it had lasted 
for a whole year, and could be more easily explained in almost any other way. 
The urine,—which with an almost free diet amounted to about three liters, of 
high specific gravity, and contained six per cent, of glucose and a trace of 
albumin,—after fermentation of the glucose and precipitation of the combined 
glycuronic acids with lead acetate and ammonia, deflected the ray of polarized 
light to the left only slightly (0.2 0 with Hoppe-Seyler’s instrument), and 
yielded a moderately pronounced Gerhardt’s reaction. On account of the 
presence of but a small amount of / 3 -oxybutyric acid, I considered it not 
dangerous for three days to exclude carbohydrates from the food. The patient 
received an abundant food in eggs, fish, different meats, and butter—a seem¬ 
ingly much better diet than her poor fare at home, chiefly consisting of herring 
and potatoes. After three days, when I had found out how much glucose was 
being excreted with the strict diet, the patient was to receive 60 grams of white 
bread and a considerable amount of vegetables every day. 

Polyuria and glycosuria quickly diminished, but Gerhardt’s reaction became 
much more marked, even comparatively, and during the night of November 
2d-3d violent diarrhea began. When I visited the patient on the morning 
of November 3d, coma evidently was threatening. Respiration was blowing 
and dyspneic, the pulse 120, the temperature in the rectum 35 0 C. (95 0 F.) in 


DIABETES INFANTILIS. 


157 


the morning and 34.4 0 C. (93.9 0 F.) in the afternoon. The patient was given 
brandy in strong tea, together with eggs, biscuits, and enormous quantities of 
sodium bicarbonate water. When she could eat no biscuits, and no levulose 
could be had, I gave her cane-sugar in my anxiety to increase the carbo¬ 
hydrates. Marked improvement followed, and when the danger of coma 
seemed much diminished, some opium was given for the diarrhea. The 
patient improved greatly. On November 7th the pulse was 84, the temperature 
36.8° C. (98° F.), respiration almost normal, the sensorium and intelligence 
seemed quite free, and I began to hope that I should escape too severe con¬ 
sequences of this ill-timed dietetic system, still defended by powerful 
authorities. Diarrhea, however, again began on November 8th, and the 
patient became more and more comatose, and died on November 16th. Dur¬ 
ing the period of coma the glucose sank to 0.7 per cent., the urea to 0.35 per 
cent., the chlorids likewise to a minimum, and the specific gravity to 1.013. 
The phosphoric acid decreased less, and was 0.1 per cent. The temperature, 
which before had constantly been somewhat below the normal, during the last 
days went up to 38° C. (ioo° F.) in consequence of the pulmonary lesion. 

On postmortem examination the muscles were found dry and atrophic, the 
dura somewhat thickened, the pia distended with edema, the heart small, 
pale, and flabby, while the right lung contained a caseous focus. The liver 
was partly in a state of fatty degeneration and partly exhibited rose-red spots 
’ and an appearance suggestive of the nutmeg-liver. The pancreas was in 
every respect normal. The kidneys were large, flabby, pale, with the cortex 
somewhat discolored. The spleen was normal. A strong smell of acetone 
filled the room. 


CHAPTER V—DIABETES INFANTILIS * 

The pathologic excretion of glucose is much rarer in children 
than in adults, and almost always represents either a simple, trans¬ 
itory glycosuria from some accidental cause, or a severe diabetes, 
which may lead to death in the course of a few weeks, and hardly 
ever fails to do so in the course of a few years. Still, in excep¬ 
tional cases it happens that a child suffers from protracted dia¬ 
betes in the mild stage. 

* Niedergesass (1873), Redon (1877), Kiilz (1878), Leroux (1880), Stern (1889), 
and others have written on Diabetes infantilis. 





153 


DIABETES MELLITUS AND GLYCOSURIA. 


Simple glycosuria in children generally occurs in conjunction 
with neuroses and with the infectious fevers, but it may arise from 
any cause that has the same effect in adults. It has been observed 
by a number of clinicians in cases of diphtheria, scarlet fever, and 
measles, and also in cases of epilepsy, chorea, supraorbital neuralgia 
(Franque, Goolden, and others). In cases of pertussis and croup 
it may be the result of asphyxia (Laborde). Lecoq mentions the 
appearance of from o.i to 0.2 per cent, of glucose in the urine of 
healthy children who had eaten sweets (? ?). Parrot found glucose 
in more than one-third of all athreptic children, especially in those 
that were cyanotic. I have several times found distinct traces of 
glucose in boys that had been addicted to masturbation. I believe 
that in many such cases true diabetes may develop in middle age, 
though one may see glycosuria disappear in other cases. Pro¬ 
tracted glycosuria is much rarer, and is of much greater significance 
in children than in adults.* 

True diabetes is so rare in early childhood that many an expe¬ 
rienced children’s physician and many a specialist in diabetes have 
never seen a diabetic patient under ten years of age. Romberg 
observed among 5900 infant patients but a single case of diabetes. 
Schmitz encountered among 2115 cases of diabetes 10 patients in 
the first and 75 patients in the second decad of life. 

Prout saw among 700 cases of diabetes one child under five 
years old.f It is only by mere accident that in the course of little 
more than a year (1895-1896) I have been consulted in four cases 
of diabetes in children under ten years of age, while previously I 
had seen but a single such case. On the other hand, I have seen 
a not inconsiderable number of cases in children between ten and 


* Cantani urges the necessity of looking for glucose in cases of nocturnal enuresis. 
If one does so, and in the presence of a reducing-substance verifies it as glucose by the 
fermentation-test, he will find that in the great majority of the common cases of nocturnal 
enuresis the urine is free from glucose. 

f I have, unfortunately, taken notes of my diabetic cases only during recent years, 
and do not know their number ; but my 5 cases of diabetes in children under ten years 
occurred—one in a girl six years old, in the central part of Sweden ; another in a girl four 
years old, in Stockholm ; 2 boys of four and of nine years, respectively, in Stockholm; 
and one boy of four years, in New York. For two of my cases in Stockholm and for 
the case in New York I am indebted to my esteemed friends, Dr. Nettelbladt and Dr. 
Kinnicutt, respectively. 



DIABETES INFANTILIS. 


159 


fifteen, and some in girls and boys between fifteen and twenty years 
old. Statistics show that the third quinquennium of life,—viz., from 
ten to fifteen years,—of the first four quinquenniums is that in which 
diabetes occurs most frequently. In the period from fifteen to 
twenty years diabetes again becomes rarer, while from the latter 
age it continues to grow more frequent. 

It is of great interest to see how the total frequency increases, and how the 
greater frequency among boys than among girls shows itself from the second 
decad, in which both sexes begin to be somewhat strained intellectually, and 
in which, unfortunately, sexual excesses (masturbation) among boys already 
begin to become frequent. Among 136 cases of diabetes up to the age of fifteen 
years, there were 27 cases during the first, 32 during the second, and 77 during 
the third quinquennium of life (Leroux). Pavy has observed 5 girls and 3 boys 
in the first, and 35 boys and 22 girls in the second decad of life. 

In children under ten the relative frequency in the two sexes differs from 
the analogous figures later in life. In adults the ratio between diabetic men 
and diabetic women is best represented by the figures 3:1. But among dia¬ 
betic children under ten years of age we find at least as many girls as boys. 
Among 102 cases at this period there were 57 girls and 45 boys. Leroux alone 
has observed what he calls a “ statistique favorable aux gar^ons” : namely, 22 
boys and 16 girls. Kiilz’s and Leroux’s figures from different sources and my 
own 5 cases make up the usual small majority for the girls in early childhood : 
75 girls and 70 boys. 

The causes are, of course, the same for children as for adults, 
but there is some difference in their relative efficiency. Hereditary 
influence is exceedingly important in childhood. Isenflamm, as 
early as 1784, mentions an instance of diabetes in 7 brothers, who 
all died at the age of seven or eight years. Roberts observed 8 
diabetic children in the same family; Watson, Bence-Jones, and 
West each saw 3 ; and in India such cases are common. I am in¬ 
clined to believe that infectious diseases are the most frequent acci¬ 
dental cause of diabetes in children ; in adults emotions and mental 
sufferings play a much more important role. Trauma is the cause 
of a greater percentage of infantile than of other cases. Finally, 
both from reports in literature and from two of my own cases, I am 
inclined to believe that starvation is a relatively more frequent cause 
in childhood than later in life (Andral, Heine, Senator, Ingerslev, 
and others have seen such cases). 

Infantile diabetes usually is like the worst cases in adults, and 
presents itself as a terrible dystrophy with a rapid course. It 


i6o 


DIABETES MELLITUS AND GLYCOSURIA. 


is especially in these cases that one sometimes hears the date of 
the attack named. “ The 20th of April my boy was in perfect 
health ; the 21st he was very ill, and drank as much as he could 
the whole day,” the father of a four-year-old diabetic boy told 
me some time ago. The little victims suddenly stop playing and 
become quiet and drowsy, irritable and peevish. The diabetic 
symptoms rapidly reach a maximum of intensity. There are on 
record reports of cases in which sixteen liters of urine and one kilo¬ 
gram of glucose were secreted in the twenty-four hours. The 
urine usually is pale, greenish-yellow in color, and of high specific 
gravity. In a case seen by Redon the latter was 1.070. Ger- 
hardt’s reaction is often distinct from the beginning. In a few 
months the cavity of the mouth may present a furrowed tongue, 
partly with a thick, brownish covering, partly with fleshy, flayed- 
looking patches, and carious teeth ; it often becomes the seat of a 
luxuriant vegetation of Oidium albicans. The soft, diabetic cataract 
may develop in an amazingly short time, and at quite an early age. 
In one of my cases, to be related later, the patient was fourteen 
years old. The face is either pale or it may present a circumscribed, 
cyanotic, red discoloration on the cheeks; the skin is dry and 
squamous. Girls suffer from vulvitis, boys from phimosis and balano- 
posthitis. The loss of flesh can not be checked, and the children 
become exceedingly weak and have to keep their beds. The tem¬ 
perature, apart from febrile complications, keeps below the nor¬ 
mal, but even in these cases rarely below 36° C. (96.8° F.). 

The prognosis is extremely bad, and I do not know that in any 
of the typical infantile cases the patient has returned to health.* 

In cases of diabetes in the first decad of life death often takes 
place within a year; a longer duration than two years after the 
first appearance of symptoms at this age is rare, and the rarer, the 
younger the patient. In some cases the dystrophy leads to death 


* There are many reports of complete recovery even from infantile diabetes. Of 96 
cases from II different writers I find 83 with a fatal issue and 13 in which recovery 
ensued. These reports are as unreliable as the analogous ones concerning adult cases. 
But as in cases of diabetes from infections and from trauma the prognosis is better than 
in other cases, and as these causes are relatively frequent in infantile cases, I presume 
that true diabetes in a child—which may be a mild diabetes—now and then has dis¬ 
appeared. 




DIABETES INFANTILIS. 


161 


in a few weeks. The fatal issue in most cases is brought about by 
coma or marasmus.* 

As infantile cases are comparatively rare, I record here one of my own from 
each of the four first quinquenniums. 

Ellen W., four years old, had an insane aunt. The father is very “reli¬ 
gious.” On December 16th I was called to see the child, and on asking about 
the duration of the disease the mother answered : “ She fell ill the 5th of 
November.” 

The girl was pale and almost only “ skin and bones.” The tongue already 
presented the diabetic type, the teeth were carious, and the breath smelled of 
acetone. Thrush reappeared in several places constantly as quickly as it was 
got rid of. The child was irritable, but otherwise drowsy ; a certain degree of 
poisoning was already manifest. The reflexes were extinguished. Severe 
epigastric pain caused the patient to cry out with anguish. The pulse was 80, 
the temperature in the rectum 36.2° C. (97.2° F.). 

The child received about 75 grams of bread with her food. The urine ex¬ 
creted amounted to 2500 cu. cm., had a specific gravity of 1.040, and yielded a 
pronounced Gerhardt’s reaction, some /?-oxybutyric acid, and a large quantity of 
glucose. The introduction of this allowance of carbohydrate after the previous 
strong restriction was followed by decided improvement; coma, however, was 
only put off for four weeks. No postmortem examination was held. 

B., a boy nine years old, had a “ nervous ” mother, two insane aunts, and 
an uncle who died by suicide. (There are, however, reasons for suspecting the 
boy’s diabetes to be of pancreatic origin. See below.) 

About a year before the child came under my observation he began to wet 
his bed, and the family physician found an abundant quantity of glucose in the 
urine. 

When I saw the boy on April 1, 1896, he was in an exceedingly miserable 
state. His appetite was voracious. He had, however, lost a great deal of 
weight, and the outlines of the wasted muscles were distinctly to be seen 
through the dry, atrophic skin. The mental state had lately gone from bad to 
worse, and the boy, who had previously been of a gentle disposition and of 
quite excellent parts, was now usually apathetic, but on the slightest provoca¬ 
tion was subject to attacks of violent rage, followed by deep depression. Sleep 
rarely came before three in the morning. After exertions attacks of general 
clonic spasms occurred, with full consciousness. A continuous headache exacer- 


* In 21 cases collected by Redon from different writers there were 9 deaths from 
marasmus without coma, 3 from marasmus with coma, 4 from pulmonary tuberculosis, 3 
from acute inflammation of the lungs, and 2 from cerebral affections. Concerning these 
statistics, it may be remarked that the number of deaths attributed to coma is doubtless 
much too small; coma seems to be the most frequent mode of death in cases of infantile 
as well as those of other severe forms of diabetes. 



i62 


DIABETES MELLITUS AND GLYCOSURIA. 


bated in the morning and in the evening. Sciatica was present on both sides. 
The knee-jerk was slight on the left, but almost normal on the right side. On 
the left leg sensibility was distinctly diminished. Psoriasis was present on both 
knees. Vision was normal. The pulse was 66, the temperature in the rectum 
2 , 7 - 3 ° C. (99 0 F.). Later, the patient’s mental state did not permit thorough 
examination. 

The feces consisted partly of white-colored fatty masses. (Were it not for 
this symptom, one might be inclined, on account of the strong neurotic in¬ 
heritance, to consider the case one of neurogenic diabetes.) 

After considerable though not absolute restriction of carbohydrates a large 
sample of urine was found to have a specific gravity of 1.038 and to contain 
6.6 per cent, of glucose, some diacetic acid, but not an appreciable amount of 
/ 3 -oxybutyric acid. The disease, which probably for some time had kept within 
the light stage, had lately, according to a chemist’s calculation, caused a loss of 
nearly one kilogram of glucose a day. The maximum measured quantity of 
urine in my observation, however, did not exceed eight liters. 

The boy had previously lived on a more or less rigid diet, but on account of 
his despair with regard to his food some concessions had lately been made. 
The state was such that none of the three physicians who saw him believed 
that his life would be spared for more than a few weeks. The treatment now 
was directed chiefly against the nervous symptoms. The diet was changed, 
and the patient was allowed to eat as much bread as he wished, and green vege¬ 
tables and levulose were added to his bill of fare. The polyuria and the poly¬ 
dipsia, of course, increased at once, but the mental and general state improved 
manifestly, and the hitherto continuous loss of flesh stopped. To our amaze¬ 
ment the patient lived not only through the whole of 1896, but also through 
the greater part of 1897, and died in October of that year, not from coma or 
marasmus, but from a carbuncle on the head. I did not dare to ask for a post¬ 
mortem examination. 

It is my firm opinion that any considerable restriction of carbohydrates 
would have led to a much earlier death, though I fully acknowledge the small 
value of the patient’s last year for himself and others. 

Anna Charlotta J., fourteen years old, did not know much about her family, 
but described the evident epilepsy of her sister. 

At the age of twelve the girl lived for two months as a servant with some 
poor people, and literally starved. When she again returned to the compara¬ 
tively good table of her home, she became diabetic. 

Somewhat more than two years afterward the child was admitted to Queen 
Sophia’s Hospital in Stockholm to be operated upon for typical, diabetic, soft 
cataract on both eyes (Nordenson). I found her very thin, pale, and anemic, 
with a dry, scaly skin. She was moderately depressed, somewhat irritable, 
slept fairly well, had normal knee-jerks, and felt “ creepings ” in the arms and 
legs. The teeth, though still fairly good, now began to be carious, and the 
tongue was dry and of a vivid red, while fissures formed in both angles of the 
mouth. The appetite was voracious. The liver was normal in size, consis¬ 
tency, and sensibility. The bowels were somewhat sluggish. 


DIABETES INFANTILIS. I 63 

Over the apex of the right lung in one place there was some flatness of the 
percussion-note. 

The pulse was 120 in the morning. The temperature was somewhat below 
the normal during the whole time. The weight was 28]kilograms. 

A sample of urine obtained when the patient, who had eaten whatever she 
wanted, arrived had a specific gravity of 1.046, contained 9.2 per cent, of glu¬ 
cose, was free from albumin, and yielded a dark bluish-purple reaction with 
ferric chlorid. 

During the first days the patient received 90 grams, and afterward 60 grams, 
of rye-bread, some green vegetables, and four glasses of unskimmed milk a 
day, with much butter, meat, fish, and eggs. 

The bodily weight increased from 28 kilograms on December 1st to 30 
kilograms on December 23d. Then dyspeptic troubles arose, with diarrhea 
and a loss of weight in one week of nearly two kilograms. Opium was given 
and the patient was allowed 80 grams of white bread daily. 

By January 5th the girl had regained her bodily weight and reached her 
maximum of 30.3 kilograms. The general state also was at its best. The 
daily portion of bread was again reduced to 60 grams. With this diet the 
urine amounted to from 2 to 2.5 liters and contained upward of 5 per cent, of 
glucose. Gerhardt’s reaction constantly was pronounced, as manifested by a 
rich Burgundy color; after fermentation and precipitation with ammonia and 
lead acetate the urine still deflected the ray of polarized light in Hoppe-Seyler’s 
instrument about 0.2 degrees to the left (/ 3 -oxybutyric acid). The urine from 
8 P. M. to 8 A. m. generally was a little more abundant than the urine collected 
during the day, but not rarely the contrary happened. 

On January 7th the urine for twenty-four hours amounted to 2125 cu.cm., 
and had a specific gravity of 1.034, with 4.4 per cent, of glucose. It yielded, 
as usual, a marked Gerhardt’s reaction, and, for the first time, contained a 
small quantity of albumin. 

On January 10th the patient presented the well-known prodromes of coma. 
She had been very uneasy during the night, and was then in terrible anguish, 
but intelligence and sensorium were still clear. The patient complained, at 
times with loud cries, of violent epigastric pains. The pulse was nearly 150, 
the respiration 28. The girl was given tea with brandy, liquor ammoniac, 
anisatus, a rectal injection of tepid water, a warm bath (39 0 C.) (102.2° F.), and 
general massage. The diet was unrestricted, and enormous quantities of 
sodium bicarbonate were given in soda-water. After a marked but transitory 
improvement the patient struggled on, with slight changes, until the 12th, when 
drowsiness became manifest. The epigastric pains had now stopped, the res¬ 
piration was 25, the pulse 132 ; the 2125 cu. cm. of urine had a specific gravity 
of only 1.021, with 2.7 per cent, of sugar and some diacetic acid. On January 
13th the specific gravity was 1.019 and the glucose 1.2 per cent. The patient 
remained conscious until noon, with only slightly impaired intelligence, but 
then became comatose and died quietly at 7 a. m. 

Upon postmortem examination the dura mater was found somewhat thick¬ 
ened, the pia distended by an abundant edema. The fourth ventricle and the 
aqueduct of Sylvius and adjacent parts seemed to the naked eye normal, 


164 


DIABETES MELLITUS AND GLYCOSURIA. 


beyond some perivascular spaces, such as Dickinson has described. A large 
part of the sympathetic nerves was carefully dissected, and seemed perfectly 
normal. The heart was pale and small. At the apex of the right lung was a 
caseous nucleus of the size of a pea. The pancreas was normal. The liver 
was somewhat hyperemic. The mesenteric glands were enlarged ; one of them 
was caseous. The kidneys were large and hyperemic. 

Miss G. V., nineteen years old, with a maternal neurotic inheritance, began 
to feel exceedingly thirsty in November, and consulted me January 28th. 

There was polydipsia, polyuria, and pollakiuria. The formerly gentle dis¬ 
position of the patient was changed into one of great irritability. Sleep was 
bad, and there was constant headache. The knee-jerks were very weak. 
The teeth were partly carious, partly absent. The gingiva around a molar 
tooth was swollen, and an incision was followed by the escape of a drop of 
pus ; a probe passed rather deep along the root of the tooth. The tongue 
was coated, and with a dry, bright-red apex. A strong smell of acetone was 
present on the breath. 

The patient was exceedingly anemic, and over the jugular vein a pronounced 
“ bruit du diable ” was audible. The apex of the right lung was slightly 
infiltrated. 

A specimen of urine had a specific gravity of 1.040, with 8.2 per cent, of 
glucose, a marked Gerhardt’s reaction, and a small quantity of ^-oxybutyric 
acid. 

Sixty grams of white bread and some green vegetables in the food yielded 
about 170 grams of glucose a day in 3000 cu. cm. of urine. 

At the end of May the patient died in diabetic coma. 


CHAPTER VI.—DIABETES MELLITUS FOLLOWING EXTIR¬ 
PATION OF THE PANCREAS. 

As I have mentioned, a connection between lesions of the pan¬ 
creas and the glycosuric dystrophy had long been suspected by 
many and accepted by some. Finally, in 1889, v - Mering and 
Minkowski communicated to the Association for Natural Sciences 
of Strasburg their great discovery that total extirpation of the pan¬ 
creas gives rise to severe diabetes, characterized by glycosuria 
under all dietetic conditions, polydipsia and polyuria, rapid loss of 
weight, the presence of acetone, diacetic acid, /3-oxybutyric acid, 



DIABETES MELLITUS AFTER REMOVAL OF PANCREAS. 1 65 

and an increased amount of ammonia in the urine, and death in 
diabetic coma. These admirable and successful investigators had 
discovered the only certain method yet known of producing “ arti¬ 
ficially ” true severe diabetes. They had, further, studied this form 
of diabetes conscientiously. Minkowski afterward continued the 
researches in a careful and extensive scientific investigation. About 
the same time De Dominicis, in Italy, independently of others, also 
observed (in dogs) diabetes after extirpation of the pancreas. 

Later, Aldehoff, Sandmeyer, Lepine, Hedon, Gley, Thiroloix, 
Chauveau and Kaufmann, Gaglio, Caparelli, and others made re¬ 
searches on diabetes after extirpation of the pancreas. Unfortu¬ 
nately, these researches have on many points led to such different 
results that definite conclusions are at present impossible, though, on 
the other hand, many important facts have been added to our stock 
of knowledge. 

Diabetes mellitus following extirpation of the pancreas has been 
observed in dogs, cats, and hogs (v. Mering and Minkowski), 
hawks (Langendorf), falcons (Weintraud), geese (Kausch), turtles 
and frogs (Aldehoff, Marcuse, Velisch). Kausch observed the 
extremely interesting fact that in birds hyperglycemia may reach 
much higher figures—up to 0.5 per cent.—than in mammals with¬ 
out causing glycosuria. This doubtless is the reason why the 
urine after operations on birds (pigeons and ducks) has sometimes 
been found free from glucose. The normal glycemia in birds 
seems to amount to only 0.14 or 0.15 per cent. (Kausch). 

For the details of the operation reference may be made to the 
special works. The technical difficulties are quite considerable, and 
the object of the experiment is often frustrated by necrosis of the 
duodenum and other complications. The French experimenters 
have generally injected paraffin, asphalt, etc., into the pancreatic 
duct, resulting in atrophy and induration of the gland, and a 
couple of weeks afterward they have performed the operation of 
extirpation. 

I here follow chiefly Minkowski; the facts, when no mention is 
made to the contrary, refer to the dog. 

Glycosuria generally begins a couple of hours, sometimes much 
later, after the operation ; in 50 per cent, of the cases it appears 
within five hours (Lepine). It generally reaches its maximum on 


1 66 DIABETES MELLITUS AND GLYCOSURIA. 

the third day, with from io to 12 per cent.* of glucose in about 1.5 
liters of urine. The hyperglycemia may reach 0.9 per cent., but 
rarely exceeds 0.5 per cent. As already mentioned, the relation be¬ 
tween the hyperglycemia and the glycosuria is not a fixed one, and 
some influence on the part of the kidneys must be admitted. If the 
animals escape other complications, the glycosuric dystrophy leads 
in a few weeks to diabetic coma. 

If any considerable part of the pancreas—one-eighth or one- 
twelfth—is left, diabetes does not result. Hedon found the reten¬ 
tion of even about one-thirtieth sufficient to prevent the develop¬ 
ment of the glycosuria. By leaving a small part of the gland one 
may restrict the effect to a slight glycosuria or to a mild diabetes, 
and it has been found that all the different stages of the glycosuric 
dystrophy may be effected by resection of the pancreas. 

Chauveau and Kaufmann have found that if the spinal cord is 
divided in the lower cervical or upper thoracic region before extir¬ 
pation of the pancreas, the operation is not followed by glycosuria. 
I shall recur later to their experiments and conclusions. 

Hedon and Thiroloix both are of the opinion that a gradual and 
slow destruction of the pancreas (by injections of different sub¬ 
stances into it) may take place without causing glycosuria (?). 

Fever diminishes and phloridzin increases the glycosuria follow¬ 
ing extirpation of the pancreas. 

The sugar in the urine has been proved to be glucose, not mal¬ 
tose. 

When carbohydrates are excluded from the food after total 
extirpation of the pancreas, there gradually arises a fixed relation 
between the glucose and the nitrogen in the urine, a relation which 
is represented by the figures 2.8:1. When carbohydrates are 
given, it seems that during the highest intensity of the dystrophy 
all the glucose produced is excreted, and this fact and the fixed 
relation between the glucose and the nitrogen in the urine during 
exclusion of carbohydrates would—if one does not accept the 
presence in the blood of a “materia peccans ”—seem to indicate 
that with the destruction of the pancreas something is lost to the 
organism that is necessary for the combustion of every molecule 


* Hedon, by giving only bread as food, increased the glycosuria to 22 per cent. 



DIABETES MELLITUS AFTER REMOVAL OF PANCREAS. 1 67 

of glucose. During other periods of the diabetes following total 
extirpation of the pancreas, however, according to all researches, a 
certain part of the ingested glucose is used up in the organism. 
Then,—though the conditions for the production of glucose from 
proteids are not fully known,—theoretically, out of ioo grams of 
proteid, minus the carbon necessary for the production of urea, 
there might be produced 213 grams of glucose and only 16 grams 
of nitrogen— i, e., much more than only 2.8 times as much glucose 
as nitrogen. 

It thus seems that though the pancreas is proved to have a 
specific function in the utilization and combustion of glucose, it 
may not be alone concerned in this phase of bodily activity. 

Minkowski, after giving large amounts of levulose, observed 
increased glycosuria, but found that a smaller part of this mono- 
saccharid had passed unchanged into the urine. After 200 grams 
of levulose by the mouth the urine contained 105.6 grams of 
glucose and 15.6 grams of levulose. There were 7.8 grams of 
nitrogen, so that 21.84 grams (7.8 X 2.8) of glucose were derived 
from proteids. The rest—83.76 grams of glucose—was thus 
derived from the levulose. 

Minkowski failed, after giving considerable amounts of maltose, 
saccharose, and lactose, to find any of these disaccharids in the 
urine unchanged, probably because the quantities were not large 
enough ; in fact, none of them seems to have been given in as 
large amount as the levulose. The glycosuria was increased by 
all three of the disaccharids. 

After extirpation of the pancreas the animals quickly lose flesh, 
sometimes in the course of a fortnight losing more than one-third 
of their bodily weight. This is a necessary effect of the deficient 
digestion and of the enormous glycosuria. Abelmann found 43 
per cent, of fat ingested in emulsion, almost all other fat and 56 
per cent, of ingested proteid in the feces, which also contained 
large quantities of undigested bread. Kaufmann found that dia¬ 
betic dogs of from 8 to 1 5 kilograms in weight, subjected to abso¬ 
lute starvation, lost from 250 to 500 grams in weight a day, while 
normal dogs of the same size under similar circumstances lost only 
between 160 and 175 grams. 

Glycosuria and impaired digestion, according to the opinion of 


1 68 DIABETES MELLITUS AND GLYCOSURIA. 

most investigators, are not the only causes of autophagy in these 
and in other cases of severe diabetes. A third cause is the almost 
universally accepted protoplasmic , toxic disintegration of the proteid 
cellular substances of the organism. 

Minkowski failed in some cases after total extirpation of the pan¬ 
creas to find diacetic acid and /S-oxybutyric acid in the urine, both 
of which, so far as my experience goes, are constantly found in 
equally severe cases in man. Further investigations in this respect 
seem necessary, but it is possible that the production of these acids, 
which certainly are in some way connected with the excretion of 
glucose produced by proteids, is governed by other conditions in 
the dog than in human beings. The diabetic animals completely 
oxidize ingested acetone (Schwarz), but the ingestion of diacetic 
acid (Schwarz) and of y3-oxybutyric acid (Minkowski) is followed 
by acetonuria. 

The lactic acid in the muscles was found to be greatly dimin¬ 
ished. The glycogen was also greatly reduced in the liver and in 
the muscles—probably on account of the acidosis, which in most 
cases was quite pronounced. Syzygium jambulanum had no de¬ 
creasing effect upon the glycosuria. 

The diabetes following extirpation of the pancreas is a direct 
effect of the removal of the gland. It does not result from the 
absence of the pancreatic juice, for ligation of the pancreatic duct or 
the production of a fistula through which the juice is conducted 
outside the organism causes no diabetes. Neither does the dys¬ 
trophy result from a lesion of the solar plexus, as has been sup¬ 
posed. Minkowski proved this theory to be false by leaving a part 
of the pancreas in connection with its vessels outside the perito¬ 
neal cavity under the skin, without the development of diabetes, 
while subsequent removal of this remaining piece of pancreas was 
followed by the customary diabetes. 

Either the removal of the pancreas causes something to disap¬ 
pear from the blood that is necessary for the normal combustion 
and utilization of the sugar, or it causes something to remain in the 
blood that prevents the combustion and utilization of sugar. 

It has been proved that injection of diabetic blood into the veins 
of a healthy animal does not produce even transitory diabetes. On 


METABOLISM AND NUTRITIVE NEEDS. 1 69 

the other hand, it was shown by Claude Bernard that the normal 
blood contains something that causes the sugar in it to disappear 
after it has been for some time outside the organism. These facts 
have led many to the acceptance of a theory that extirpation of the 
pancreas causes diabetes by removing something that is produced 
in the pancreas as an “internal” secretion and is given up to the 
blood, where its presence is necessary for the combustion of the 
sugar. Lepine and his disciples, and even some of his antagonists, 
found that the blood of dogs, diabetic after extirpation of the pan¬ 
creas, both within and without the organism, loses its sugar less 
quickly than does normal blood. Kausch saw an analogous 
phenomenon in birds. Schwarz found that, though dogs after extir¬ 
pation of the pancreas seem to oxidize as large amounts of acetone 
as normal dogs, the former, diabetic dogs, unlike normal dogs, 
after ingestion of diacetic acid exhibited acetonuria. All this has 
strengthened the position of those who consider diabetes an effect 
of decreased consumption of sugar. In the next chapter we shall 
find that, even if these observations are correct, they alone do not 
settle the question of the immediate causes of diabetes—a question 
the solution of which is one of the most difficult and complicated 
tasks that are at present engaging the attention of students of experi¬ 
mental pathology. 


CHAPTER VII.—METABOLISM AND NUTRITIVE NEEDS. 

Notwithstanding the progressive strides that have been made 
in recent years, the metabolic changes that take place in diabetes 
are but imperfectly known. 

By following as well as we can the carbohydrates, the fat, and 
the proteids on their way through the organism we may, however, 
obtain a conception of the respective processes, which is not with¬ 
out considerable theoretic and practical value. In doing this we 
must not omit to give some attention to corresponding processes in 
normal organisms ; neither must we lose sight of the differences 


12 



I/O DIABETES MELLITUS AND GLYCOSURIA. 

between cases of mild and severe diabetes— i. e., between the patient 
that excretes sugar only after ingestion of carbohydrates and the 
one that exhibits glycosuria at the expense of proteids, and with a 
diet consisting exclusively of these and of fat. 

We have already seen that in the great majority of diabetic 
cases digestion is perfectly normal. In such cases Pautz recently 
found 7.59 per cent, loss of nitrogen and 3.54 per cent, loss of fat. 
The maximum and minimum figures for nitrogen were 12.97 and 
1.74; for fat they were 9.12 and 1.06— i. e., just about what we are 
accustomed to see designated as normal. As to carbohydrates, 
Heller, as early as 1852, showed that they are, as a rule, normally 
digested in cases of diabetes, and Hirschfeld’s cases prove that this 
often takes place, even when digestion of proteids and fat is im¬ 
paired. Of ingested starch, normally from 1 to 7.4 per cent, 
appears undigested in the feces. 

The normal changes that carbohydrates undergo in the alimentary canal 
must be borne in mind. Starch (or glycogen) digested by the mixed saliva (or 
by the secretion of the parotid gland alone) yields achroodextrin and maltose* 
and only small quantities of glucose (Musculus and v. Mering, Kiilz). The 
diastatic ferment found in the stomach in the acid gastric juice is not very 
active; but in the duodenum the pancreatic juice is most efficient in the same 
way as the saliva. The final products, however, of the digested starch, found 
almost entirely in the portal system and only in comparatively minute quanti¬ 
ties in the lymphatics, consist almost exclusively of glucose, together with some 
traces of dextrin and maltose (C. Voit, Bleile, v. Mering), whether this result 
has been brought about by the “ invertin ” from the mucous membrane of the 
bowels (Tebb), or by the epithelium itself (Bunge), or by the blood (Bial, Roh- 
mann). 

Cane-sugar partly is decomposed into glucose and levulose, partly remains 
unchanged in the stomach, and is so far absorbed in this state; in the duodenum 
this part of the disaccharid is also quickly decomposed into its monosaccharid, 
levulose, and glucose by the pancreatic juice (Kobner). When taken in large 
amounts like all saccharids it remains unchanged for some small part as cane- 
sugar, not only in the bowels, but in its passage through the whole organism, 
and it is found as such in the urine. 

Maltose probably is already changed in the bowels into glucose (Voit). 

Lactose, so far as it is not changed into lactic acid, etc., probably remains 
in large part unchanged in the alimentary canal (Lusk); the different results 
of numerous researches seem to me to indicate great individual and accidental 


*Disaccharids and Alonosaccharids. Maltose = glucose 4- glucose. Cane-sugar = 
glucose -f- levulose. Lactose = glucose -(- galactose (Hammarsten). 




METABOLISM AND NUTRITIVE NEEDS. 


171 


variations. Lactose passes unchanged into the urine after smaller amounts 
are taken than do the other saccharids (G. Voit, Bischoff, Hofmeister, and 
others), and does often so during lactation. 

In chickens and rabbits levulose seems to be absorbed in an unchanged 
state (Fr. Voit, Lusk, Otto). Like all other saccharids, it passes partly un¬ 
changed into the urine after large amounts have been taken. 

Cane-sugar and maltose are in larger part (70 or 80 per cent.) absorbed 
during the first hour after ingestion. Glucose seems to remain a little longer, 
but lactose a less time in the stomach. 

These results are gained chiefly in dogs whose food and digestion are simi¬ 
lar to man’s. Still, there seem to be differences, and normal dogs seem to 
excrete glucose after the ingestion of large amounts of cane-sugar, which is not 
the case with man. Rubner, by feeding dogs with cane-sugar exclusively, 
found almost only this disaccharid in the urine on the first day, but afterward 
gradually more and more glucose. Seegen found in dogs after the ingestion of 
cane-sugar this saccharid in part in its unchanged state, in part as invert- 
sugar (= glucose -j- levulose), while Praussnitz made the same observation in 
chickens. 

Lusk obtained the following results six and one-half hours after the inges¬ 
tion of 30 grams of cane-sugar by rabbits : 


- 

Cane-sugar. 

Glucose. 

Levulose. 

Stomach,. 

0.269 

1.498 

0.858 

Duodenum and jejunum, . . 

0.002 

Traces. 

Traces. 

Cecum, . 

0. 

0.846 

1.321 

Colon and rectum,. 

0. 

Small amounts. 

Small amounts. 


With regard to the digestion of fat it must be remembered that during an 
abundant supply of easily digestible quality, often only 1.5 per cent., rarely 
more than from 4 to 6 per cent., is lost; that fat with a low-melting tempera¬ 
ture is absorbed better and more quickly than fat with a high-melting tempera¬ 
ture (Muller and Arnschink); that the presence of free fatty acids facilitates 
absorption,'in which process both bile and the pancreatic juice are of great 
importance, if the fat is not ingested in a state of emulsion (Levin, Buchheim); 
that a mixed diet promotes absorption, though the most advantageous relation 
in the quantities of the different kinds of food has not yet been determined 
(Rosenheim, Munk). Finally, it is known that catarrhal conditions first impair 
the absorption of fat, while proteids and carbohydrates still continue to be 
absorbed normally (Fr. Muller). Individual and accidental circumstances have 
a great influence even under normal conditions. 

We shall here entirely pass over the highly complicated chemic processes 
by which the ingested proteids are converted ultimately into albumoses and 
peptones, as well as the manner in which these substances are absorbed in con¬ 
sequence of the specific cellular activity of the mucous membrane. There are 



























172 


DIABETES MELLITUS AND GLYCOSURIA. 


in this respect no known or even suspected differences between the diabetic 
and the normal individual, nor in the processes by which the albumoses and 
the peptones are again changed into true albumin in its different modifications. 
According to differences in the quality of the food, from 3 to 5, or from 6 to 10 
per cent., or even more, of the proteids may normally remain undigested in 
the intestines (Rubner). During the passage of proteids through the aliment¬ 
ary canal there are formed, as is known, many substances that are not proteids 
(leucin, tyrosin, tryptophan, amido-acids, asparagic acid); in the colon and 
rectum are found a whole series of “ aromatic ” substances and other products 
of putrefaction (indol, skatol, parakresol, phenol, phenyl-propionic acid, 
phenyl-acetic acid, paraoxyphenyl-acetic acid, hydroparacumaric acid, free 
fatty acids, carbonic acid, marsh-gas, hydrogen sulphid, etc.). Often secret¬ 
ing a smaller amount of bile than normal, and partaking of food rich in pro¬ 
teids and often suffering from habitual constipation, which allows of a longer 
period for putrefactive process, diabetics are likely to produce large quantities 
of the aromatic substances mentioned. In consequence their urine usually 
contains large quantities of “ ethereal ” combined sulphates resulting from 
the oxidation of the “aromatic” substances.* 

When with an ordinary diet the ingested carbohydrate, changed 
into glucose (together with some small quantities of dextrin, 
maltose, and perhaps still other carbohydrates), is carried by the 
blood in the portal vein to the liver, it there forms the anhydrid of 
glucose or glycogen,f and to this most important substance we 
must devote a good deal of attention. 

It seems certain that not all the glucose carried by the portal vein 
to the liver is, under all circumstances or at once, transformed into 


* The phenols, skatol, and indol are oxidized in the organism and pass into the urine 
as indoxyl-sulphuric and skatoxyl-sulphuric acids. The quantity of these and other 
ethereal sulphates normally equals about 0.25 gram a day, and bears a ratio to the sul¬ 
phuric acid of the sulphates of I : 10 (from I : 15 up to I : 67). 

t Glycogen, as is well known, is a polysaccharid closely related to starch ; its formula 
probably is 6(C 6 H 10 O 5 ) -J- H 2 0 (Kiilz). Under the influence of dilute acids it is entirely 
changed into the monosaccharid glucose; saliva and pancreatic juice transform it into 
achroodextrin, maltose, and small quantities of glucose. In the cells of the liver gly¬ 
cogen is uniformly diffused in small granules embedded in larger granules of the so-called 
paraplasm (Kupfer), an imperfectly known substance, probably representing a form 
intermediate between glycogen and its mother-substances. The muscles constitute the 
other important repository of glycogen, containing about as much as the liver; it is 
present in the interfibrillary substance (Frerichs). From whatever substance glycogen is 
formed it is itself completely homogeneous (Salomon, Luchsinger, Otto). Still, there 
is some difference between the glycogen of the liver, which is colored brownish-red by 
tincture of iodin, and the glycogen of the muscles, which with the same tincture 
develops rather a violet color. 



METABOLISM AND NUTRITIVE NEEDS. 


173 


glycogen. After the ingestion of large amounts of glucose even 
normal individuals excrete some glucose in the urine. Under ordi¬ 
nary and normal circumstances a considerable part of the glucose 
may also pass through the liver and be either used immediately in 
the tissues or stored as glycogen in the muscles or elsewhere, or it 
may return to the liver and be stored there after having passed 
through the whole circulation. It is certain that the glycogen in 
the liver continues increasing for a much longer time after the in¬ 
gestion of carbohydrate than the glucose needs to pass through the 
whole organism. After the ingestion of a large amount of glucose 
the glycosuria appears within thirty or forty minutes ; after the in¬ 
gestion of syrup the maximum amount of glycogen in the liver is 
reached (in rabbits) only after from sixteen to twenty hours (Kiilz). 
After the ingestion of small amounts six hours, and after the in¬ 
gestion of large amounts from twelve to sixteen hours, elapse before 
this maximum is reached in chickens (Hergenhahn). The liver 
generally stores its maximum long before the muscles acquire 
theirs ; after the ingestion of very large amounts, however, the 
glycogen is stored about as quickly by the latter as by the liver 
(Hergenhahn). 

Glycogen is formed in the liver from both carbohydrates and 
proteids, and its amount can be maintained or increased there by 
many different substances. Glucose and levulose (or starch) yield 
the highest values, up to 20 per cent, or even more. Those sac- 
charids that do not ferment with yeast do not yield more than a 
small percentage. 

The researches on the formation of glycogen, since its discovery in 1857, 
already represent an enormous amount of work, and the subject certainly will 
be the object of further investigation. The experiments consist in subjecting 
the animals to starvation until the glycogen is supposed to be wholly con¬ 
sumed, in feeding them afterward with the substance in question, and, finally, 
in determining the quantity of glycogen in the liver. 

Bernard proved that both carbohydrates and proteids— i. e., meat and 
fibrin—produce glycogen, Woroschiloff that the latter is formed from glue. 
[That carbohydrates are formed from proteids can be demonstrated to any one 
who does not accept their formation from fat by the fact that diabetics in the 
severe stage continue for months to excrete more glucose than can possibly be 
made up by the carbohydrates in their food.] Kiilz’s “ Beitrage zur Kenntniss 
des Glycogens,” Marburg, 1891, contains a good exposition of what has been 
done in this connection by Bernard, Stokvis, MacDonnell, Tcherinoff, Hoppe, 


174 


DIABETES MELLITUS AND GLYCOSURIA. 


Doch, Weiss, Luchsinger, Naunyn, Nencki, Wolfberg, v. Mering, Finn, 
Pfluger, Hergenhahn, Nebelthau, and by Klilz himself, who fed chickens with 
muscle, fibrin, casein, serum-albumin, and egg-albumin. The last-named thus, 
beyond a doubt, proved that these substances yielded from i to 2.5 per cent, of 
glycogen in the liver. Pavy (in rabbits) with starch and cane-sugar succeeded 
in depositing 27.6 per cent, of glycogen in the liver; with starch, cane-sugar, 
and albumin the amount was 17 per cent. Meat yielded at the utmost 7 per 
cent., gum-arabic 9 per cent., gelatin traces, and olive oil also only traces 
(probably remaining from before the experiment). MacDonnell’s, Tcheri- 
nofif’s, and Seegen’s experiments led to similar results. Seegen besides found 
1.67 per cent, of glycogen in the liver of dogs after eight days without food, 
and after feeding the animals during the following eight days exclusively on 
fat in large quantities he found 0.93 per cent. Kiilz, in chickens fed with cane- 
sugar, found 8.24 per cent.; with glucose 6.63 per cent.; with levulose 6.07 per 
cent.; with galactose 3.28 per cent., and with lactose 2.32 per cent, of glycogen 
in the liver. Kausch and Socin (1898) have found as much as 9 per cent, with 
lactose. 

It will thus be seen that the power of the different saccharids to 
form glycogen in the liver in normal individuals does not bear any 
relation to their power of causing glycosuria in diabetics. Glucose 
and levulose normally yield about the same amount of glycogen, but 
glucose causes much greater glycosuria in diabetes than does levu¬ 
lose. The glycogen in the liver in diabetics again is increased in much 
greater degree by levulose than by glucose (Sandmeyer)—a quality 
of the levulose, which presumably is the cause for its producing less 
glycosuria in such individuals. The more easily a saccharid under¬ 
goes fermentation the more glycogen it forms normally, according 
to C. Voit; the less it normally passes into the urine, according to 
Cremer ; and the better it forms fat, according to Liebig. 

It is in many respects interesting to learn the effect of subcuta¬ 
neous injections of different saccharids. Fritz Voit, in 1896, made 
such injections (of ten per cent, solutions) of monosaccharids : levu¬ 
lose, galactose, and glucose ; and of the disaccharids : maltose, lac¬ 
tose, and cane-sugar. All of the monosaccharids were completely 
consumed in the tissues even after the injections of considerable 
amounts. After the injection of large amounts a small quantity 
appeared unchanged in the urine. Thus, the injection of 60 grams 
of glucose yielded a trace of glucose in the urine, while the injec¬ 
tion of 100 grams yielded 2.6 grams of glucose in the urine. 
Maltose, too, was readily consumed. The disaccharids, cane-sugar 
and lactose, however, were not consumed, and passed almost com- 


METABOLISM AND NUTRITIVE NEEDS. 


175 


pletely through the organism, and appeared unchanged in the 
urine. Only the monosaccharids and the disaccharid, maltose, 
whose molecules are believed to consist of two molecules of 
glucose, seem to form glycogen without being first changed. Cane- 
sugar can be stored as glycogen in the liver only after being con¬ 
verted into glucose and levulose, lactose only after being converted 
into glucose and galactose. 

Besides the substances already mentioned, Kiilz found that the following 
substances also have some power of maintaining glycogen in the liver: Raf- 
finose, glycerin, gum-arabic, sorbin, ethylene, glycol, erythrite, dulcite, man- 
nite, inosite, saccharin, isosaccharin, dextronic acid, saccharic acid, mucic 
acid, glycuronic acid, calcium dextronate, sodium tartrate, and citrate. Urea 
also yielded glycogen. Inulin yielded small quantities and olive-oil traces. 
Nebelthau found some power of maintaining glycogen in the liver in ammo¬ 
nium citrate carbonate, lactate, and formate in benzamid and formamid, in 
glycocolla and asparagin, in antipyrin, cairin, quinin, and chloral, chloramid, 
paraldehyd, and sulphonal. Ether, chloroform, and alcohol seemed somewhat 
efficient, while urethan yielded a dubious result. Cremer found that some 
glycogen formed after use of the pentoses * (xylose, arabinose, and rhamnose); 
Salkowski also found some after use of arabinose; Fraentzel obtained a com¬ 
pletely negative result from xylose. 

From the foregoing it will be understood that glycogen can be 
formed or maintained in the liver in many different ways. From 
glucose it is formed by dehydration, a comparatively large amount 
resulting. Lactose forms glycogen only indirectly, after having 
been divided into its monosaccharids; but though a large part of 
the ingested lactose may have been changed into lactic acid before 
this happens, the rest usually gives rise to the presence of quite 
considerable quantities of glycogen in the liver (Kausch and Socin). 
Olive-oil and other fatty substances, which are believed to main¬ 
tain the glycogen in the liver only by undergoing oxidation them¬ 
selves, seem to afford very little protection for it. As for the power 
of antipyrin to maintain glycogen in the liver, this must be derived 


*The pentoses do not seem to promise the diabetic patient anything. Ebstein found 
arabinose and xylose unchanged in the urine after quite small doses. Lindemann and 
May found about eight per cent, of rhamnose unchanged in the urine of normal indi¬ 
viduals. Sixty-five grams of rhamnose caused some glycosuria in a diabetic patient 
previously free from it; besides 7.27 grams of rhamnose appeared in the urine and 2.85 
grams in the feces. Rhamnose is suspected of having no wholesome influence on the 
kidneys. 



176 


DIABETES MELLITUS AND GLYCOSURIA. 


from some specific influence, and can result neither from direct for¬ 
mation nor from oxidation. 

The glycogen in the muscles is formed in and by the muscles 
themselves from the sugar of the blood. It may, perhaps, be fur¬ 
nished to them also to some small extent as glycogen. Bohm and 
Hoffmann found 0.4 per cent, in the cat; Hasse between 0.4 and 
0.9 per cent, in dogs, cats, and rabbits. Kiilz considered these 
figures somewhat too small. 

The glycogen in the liver and the glycogen in the muscles are, 
under ordinary circumstances, about equal in amount, and together 
make up the organism’s whole store of this substance, except a 
comparatively insignificant amount in other tissues. The storage 
in the liver and the storage in the muscles depend on the same 
influences, and are both increased or decreased by the same causes. 
The glycogen of the muscles manifests greater stability, and is 
slower both in increasing and in decreasing. Heat increases the 
glycogen, and rest has the same influence. By severing the cen¬ 
tral from the peripheral nervous system glycogen is stored in great 
quantity, partly on account of the paralysis of the muscles, partly, 
perhaps, on account of the withdrawal of other nervous influences 
(Claude Bernard, Nebelthau). Cold diminishes the amount of glyco¬ 
gen and is capable of causing its disappearance from both liver and 
muscles in thirty hours (Bohm and Hoffmann). Mechanical work 
is most effective in the same direction. Weiss found only about 
half as much glycogen in tetanized muscle as in the corresponding 
muscle at rest. Chauveau and Kaufmann had a similar experience. 
Rosenbaum, Demant, and Hergenhahn saw the glycogen almost 
totally disappear during the convulsions from poisoning with 
strychnin ; and Kiilz found the glycogen in both its great store¬ 
houses reduced to a minimum after a short period of starvation 
and hard work combined. Starvation decreases the glycogen. 
Kiilz, however, still found traces of it in the liver and somewhat 
more in the muscles of the dog after twenty days of abstinence 
from food. After extirpation of the liver the glycogen suddenly 
decreases in the muscles (Laves). Acids in the blood decrease 
and alkaline salts increase the amount of glycogen (Kiilz). After 
ligature of the choledoch duct with biliary stasis the glycogen dis¬ 
appears from the liver and is not formed again (Frerichs, Wick- 


METABOLISM AND NUTRITIVE NEEDS. 1 77 

ham Legg). After death glycogen disappears from the liver and 
(somewhat more slowly) from the muscles. Praussnitz, after only 
half an hour, found 75 per cent, of the original amount. Werther, 
after three hours, found scarcely anything left. This change takes 
place more quickly in a warm than in a cold room. 

In the blood the glycogen is found in the leukocytes ; a liter con¬ 
tains only about 0.01 gram (Huppert). The lymphatics also con¬ 
tain a small quantity (Frerichs). Glycogen has besides been found 
in the skin (Paschutin), in the hair-bulbs (Neisser), in the kidneys 
(Wiersma, Paschutin, Abeles, Ehrlich), in the spleen (Ploppe- 
Seyler), in the lungs (Abeles), in the testicles (Kiihne), and in new 
growths (Hoppe-Seyler, Brault). It seems to occur especially in 
inflamed tissues (Sotniskewski, Pavy, Kiihne), and during this state 
it has also been found in the brain (Paschutin), where it does not 
seem to be found normally (Abeles, Seegen, Kratschmer, Paschutin). 
Finally, it is much more abundant in embryonic than in fully devel¬ 
oped tissues (Bernard). In view of this fact, and of the further 
fact that it is found especially in inflamed tissues and in tumors of 
rapid growth, it would seem to be indicative of a condition of 
energetic cellular life. 

It may now be considered as settled that in cases of diabetes the 
amount of glycogen is diminished both in the liver and in the 
muscles. Frerichs, with admirable presence of mind, plunged a 
trocar into the liver of three submissive individuals, of whom one 
was in good health and the other two were diabetic. Although 
the stage of diabetes is not stated, it was probably an advanced one. 
It was found that between four and one-half and five and one-half 
hours after an abundant mixed meal the liver-cells of the healthy 
person contained a large amount of glycogen, while those of the 
two diabetics contained a moderate amount and a very small 
amount, respectively. Both the liver and the muscles of diabetic 
dogs contain little glycogen (v. Mering, Minkowski, Sandmeyer). 
Pieces of liver excised shortly after death in diabetic coma were 
found to contain very little glycogen (Frerichs) ; and it could not 
be found at all in the muscles of such patients (Abeles). The 
diabetic liver in a state of fatty degeneration seems to contain the 
smallest amount of glycogen (Boccardi). 

I presume that if a diabetic in the mild stage and a healthy 


i ;8 


DIABETES MELLITUS AND GLYCOSURIA. 


person receive the same food with so much carbohydrates that the 
diabetic excretes sugar in his urine, the latter will store less glyco¬ 
gen than the healthy person, and the glycogen will thus never reach 
such high figures as are reached normally after the ingestion of 
large amounts of carbohydrates. If, however, both the diabetic and 
the healthy individual receive the same food with such restriction 
of carbohydrates as to render the diabetic free from glycosuria, both 
will probably store the same amount of glycogen. The diabetic 
patient in the severe stage always passes in the urine glucose derived 
from both the carbohydrates and the proteids of the food, and from 
this cause alone he possesses but a limited power of storing glyco¬ 
gen. In the severe stage, however, this power is besides weakened 
by the acidosis, or the presence in the blood of diacetic acid and 
/ 3 -oxybutyric acid. 

At the same time that the amount of glycogen is diminished in 
the liver and in the muscles in cases of diabetes, it is increased in 
other parts and elements of the organism. Gabritschewski found 
much more marked reaction for glycogen in the leukocytes of dia¬ 
betic blood than in those of normal blood ; Minkowski observed 
the same fact in pus (0.83 per cent, in diabetics as against 0.23 per 
cent, in nondiabetics). The leukocytes partly have their own inde¬ 
pendent economy and store much glycogen from a hyperglycemic 
medium. The brain, in which glycogen is not normally found, con¬ 
tains this substance in cases of diabetes (see above). Ehrlich first 
demonstrated the deposition of glycogen in the epithelial elements 
of the kidneys. Leube found it twice in diabetic urine.* 

The enormously important questions with regard to the meta¬ 
bolism of glycogen, and with regard to the origin and significance 
of the glucose in the liver, have given rise to a variety of opinions 
and have been the subject of much controversy. The technical 
difficulties in solving these problems experimentally are very great, 
and the human obstinacy in defending per fas and nefas a position 
once taken is still greater. Even to-day three different main cur¬ 
rents of opinion may be recognized as represented by the names 
of Claude Bernard, Pavy, and Seegen. At present we are justified 


* Glycogen is besides found (in cases of diabetes) in the lungs, in the testicles (Grohe), 
pancreas, spleen (Abeles), in the heart, and in the cartilages (v. Mering, Ewald). 



METABOLISM AND NUTRITIVE NEEDS. 


179 


in saying that the theory advocated by Bernard has proved to be 
much the strongest, and that the vast amount of work performed 
since the fundamental discoveries of this great French physiologist 
and experimenter has tended to strengthen the opinion that if he 
has not demonstrated the whole truth he has certainly demonstrated 
the essential points of it. Pavy’s theory, denying entirely the phys¬ 
iologic formation of glucose in the liver and its presence for pur¬ 
poses of vital power in the blood, almost everywhere belongs to 
the past. Seegen, who denies that the glucose of the liver and of 
the blood (whose vital importance for the organism he acknowl¬ 
edges) is formed from glycogen, and who considers it to be formed 
from proteids and from fat, has gained comparatively few adherents 
to this last view, in which he deviates from Claude Bernard. 

Claude Bernard, in 1877, summed up his views on these subjects, 
his theory, confirmed and enlarged by later investigations, being as 
follows : The liver forms glycogen from (a part of) the carbohy¬ 
drates and the proteids of the food, and afterward, from this glyco¬ 
gen, under the influence of a ferment and under the vasomotor regula¬ 
tion of the nervous system, forms glucose, which, according to the 
needs of the organism, it delivers to the blood, of which glucose is 
a most important ingredient. For the production of vital force the 
glucose is then oxidized in the tissues into carbonic acid and water. 
Recent investigations, leaving many questions as to the fate of glu¬ 
cose for solution in the future, seem to confirm Bernard’s opinion 
that the glucose is led to complete combustion through the molec¬ 
ular structure of lactic acid (Kausch, Lang), and make it probable 
that another intermediate station between the glucose and its ulti¬ 
mate products, carbonic acid and water, is represented by the mole¬ 
cule of glycuronic acid (Weintraud). It has been proved and is 
universally accepted that fat is produced from the superfluous car¬ 
bohydrates, and the seat of this process is believed to be the liver. 

Of late, some persons, who may be considered authorities, have 
so far adopted Seegen’s theory as to believe that, with a deficiency 
of proteids and carbohydrates, fat may give rise to the formation of 
glucose. It seems to me that the facts that plead for such a theory 
are much weaker than those that plead against it (see below). 

The diastatic ferment in the liver, like all ferments not consist¬ 
ing of organisms, presents many mysterious points ; Dastre goes 


i8o 


DIABETES MELLITUS AND GLYCOSURIA. 


so far as to call it hypothetic. All attempts to isolate it—chiefly 
by precipitating it with alcohol after having extracted it from the 
liver with glycerin—have failed. Tiegl believes that it arises from 
the products of the disintegration of the red blood-corpuscles, while 
many believe it to be fixed to the living liver-cells.* 

In a decoction of the liver and in the precipitate thrown down by 
absolute alcohol from such a decoction again dissolved in water, 
glucose is formed at ordinary temperature, which is not the case 
with a solution of pure glycogen (Schwiening). Bernard believed 
the variations in the production of glucose to depend on variations 
in the circulation, and these on nervous, vasomotor influences. 
Bial, who considers the diastatic ferment of the liver identical with 
the diastatic ferment of the muscles, believes both to belong to and 
depend on the lymph. The diastatic ferment in the liver and in 
the blood changes starch and dextrin and glycogen, not into mal¬ 
tose, but into glucose, and also converts maltose into glucose. 
In the embryo and in the new-born child these effects, which 
vary in different species of animals, are quite weak. Sodium car¬ 
bonate and bicarbonate retard the effect of the diastatic ferment 
on glycogen (Gans). 

The sugar in the liver has been produced in substance by Kiilz, has 
been proved to be glucose, and is present in the liver during life to 
the amount of from 0.2 to 0.5 per cent. (Bernard, Seegen). 

After some knowledge on these subjects had been gained through earlier 
investigations, Claude Bernard, late in the forties, proved the constant presence 
of sugar in the blood, independently of the kind of food taken, and showed that 
it must be looked for shortly after the blood is obtained, as it soon decomposes. 
He showed that the sugar of the blood is formed in the liver, which always con¬ 
tains some, and that a piece of liver from which the sugar has been removed 
by washing soon again becomes sacchariferous. He explained this by the 
continued activity of the diastatic ferment constantly producing sugar, which 
increases when not removed by the circulation. When Pavy afterward con¬ 
sidered this process to take place exclusively after death, Bernard (as Dalton, 
Seegen, and others have done after him) showed that the liver during life also 
contained sugar, the quantity of which he (by somewhat too low an estimate) 
placed at 0.24 per cent. 


*Arthus and Hubner, however, have shown that a solution of fluorin (i : loo), 
which destroys cellular life, does not prevent the forn ation of glucose in pieces of liver. 
Schwiening believes that the proteids play some special role in the formation of glucose 
in the liver. 



METABOLISM AND NUTRITIVE NEEDS. l8l 

Nearly ten years afterward Claude Bernard and Hensen discovered the 
glycogen, determined its nature, and proved that it could be formed both from 
proteids and from carbohydrates. Bernard showed also that, if the liver is 
separated from the circulation, the sugar disappears from the blood—a fact after¬ 
ward corroborated by Bock and Hoffmann and by v. Mering. Bernard found, 
moreover, that the veins issuing from the liver and the inferior vena cava 
usually contain more sugar than the portal vein. On finding more sugar in 
the inferior vena cava than in the carotid artery, he first concluded that the 
sugar is consumed in the lungs, but, always ready to be corrected by facts, he, 
after Chauveau’s investigations, and after having himself found more sugar in 
the arteries than in the collateral veins, expressed the opinion that this con¬ 
sumption takes place in the tissues of the whole organism. Bernard showed 
that the sugar of the blood usually undergoes only slight variations in quantity, 
that it is somewhat increased after generous meals, that it gradually diminishes 
on starvation and in the febrile state, and that it disappears from the blood 
outside the organism in about twenty-four hours. Finally, Bernard found 
glycosuria after lesions of the brain in the floor of the fourth ventricle, made 
investigations concerning hyperglycemia in diabetes, and showed that glyco¬ 
suria in the dog begins when the sugar in the blood reaches from 0.25 to 0.30 
per cent. 

At about the same time Lehmann found traces of sugar in the portal vein, 
and determinable quantities of it in the veins issuing from the liver (horse). 

C. Schmidt, in 1850, without a knowledge of the results of Bernard’s inves¬ 
tigations, found sugar in the blood of cows, dogs, and cats. 

Chauveau, partly alone and partly in conjunction with Kaufmann, has, 
since 1856, contributed more than any one else to the confirmation of Bernard’s 
theories. After extensive and numerous experiments he came to the conclu¬ 
sion that the sugar in the blood is derived from the liver, that it is always pres¬ 
ent, and even after long-continued starvation does not entirely disappear ; that 
the arteries contain more sugar than the collateral veins, and that all divisions 
of the circulatory system contain about the same amount, except the veins 
issuing from the liver and the inferior vena cava, which are more saccharifer- 
ous, and the portal vein, which (except after the ingestion of large amounts 
of carbohydrates) is less sacchariferous than other vessels. 

Subsequently, Bohm and Hoffmann, Bock and Hoffmann, Bleile, Kiilz, 
Lusk, v. Mering, Ewald, Otto, Barral, Lepine, and others made investigations 
which have corroborated Bernard’s results. 

Pavy, one of Bernard’s own disciples, began at the close of the fifties his 
opposition to this greatest of French experimenters. Pavy found that the 
blood from the right heart of a living dog contained much less sugar than after 
death—an observation that is certainly correct, and is dependent on the fact 
that when the circulation gradually ceases, the districts next to the liver, where 
the formation of sugar continues even some time after death, become more 
sacchariferous. Pavy found also that bits of liver obtained from living animals 
and thrown into boiling water or subjected to freezing contained only small 
quantities of sugar, while, when exposed to ordinary temperature, they con¬ 
tained much larger quantities. This is also true, partly, perhaps, because the 


182 


DIABETES MELLITUS AND GLYCOSURIA. 


liver-cells of living animals produce, and the dead liver-cells do not produce, 
sugar, and partly because excessive temperatures diminish the influence of the 
diastatic ferment. Pavy concluded from these observations that the production 
of sugar in the liver is a portmortem phenomenon, and thatin life the sugar passes 
through the liver only under pathologic conditions, as in diabetes or after cer¬ 
tain lesions, probably in consequence of a vasomotor neurosis which leads to 
congestion of the liver with blood that has not entirely lost its arterial qualities. 
This sugar, then, may come from the glucose formed normally by ingested 
carbohydrates or from the glycogen, which customarily produces fat. Even 
Pavy has been forced to acknowledge the presence of sugar in the blood under 
ordinary conditions, but he believes it to be there only in insignificant traces and 
for no physiologic purpose, admitted, as it were, by some defect in the func¬ 
tions of the liver, escaping again through the kidneys as a trace of sugar in 
the urine. Pavy’s views have now only historic and personal interest, and are 
strenuously opposed even in Great Britain {e. g., by Dr. Noel Paton [1898] ). 
For many years, however, they exercised considerable influence. Among 
Pavy’s adherents were Schiff, Meissner, Ritter, MacDonnell, and (as late as 
1876) Lussanna. 

Seegen also was at first an adherent of this view. Then having found 
(with Kratschmer) that diastatic ferment in saliva and in the pancreatic juice 
does not change glycogen into glucose, but into another saccharid, which Mus- 
culus and v. Mering showed to be maltose, and finding in the liver no other 
substance capable of saccharifying the glycogen, he began to doubt that it was 
the source of the glucose. In a series of experiments he sought and believed 
that he had found that the glucose must be derived from other substances than 
glycogen. He found the glucose to increase in bits of liver before the glycogen 
began to decrease. Investigations on this subject, however, by Bohm and 
Hoffmann, Girard, Chittenden and Lambert, Bial, Butte, and Montuori have not 
corroborated Seegen’s results. Seegen, by various experiments, for which I 
must refer to his own works, believed also that he had proved the formation of 
glucose in the liver from peptone, a process which Lupine considers to take 
place throughout the whole organism. Hofmeister, Chittenden, Lambert, 
Neumeister, and Bial have also on this point arrayed themselves against Seegen, 
and arrived at other conclusions. Seegen believed, further, that he had found 
in 70 cases the blood of the hepatic veins always more sacchariferous than the 
blood of the portal vein, and he somewhat irrationally considered this a proof 
of the correctness of his views. In this also he has powerful opponents; both 
Bernard’s and v. Mering’s observations tend to show that after the ingestion 
of large amounts of carbohydrates the portal vein may contain a much higher 
percentage (up to 0.4 per cent.) than the hepatic veins or the inferior vena 
cava. 

It must be remembered that we here have usually to do with small differ¬ 
ences. Max Mosse found 0.107 P er cent, in the hepatic veins and 0.093 P er 
cent, in the femoral artery, which, according to Seegen, contains only slightly 
more than the portal vein. Mosse and others are in all probability right when 
they maintain that the high percentage of glucose sometimes found in the 
blood just coming from the liver is partly due to the sufferings of the animal 


METABOLISM AND NUTRITIVE NEEDS. 1 83 

during the experiment. Seegen finally remarks that, while glycogen is driven 
out of the liver by starvation, the sugar of the blood remains in unchanged 
quantity. This is decidedly wrong. Claude Bernard, Bohm and Hoffmann, 
and Otto all have shown that prolonged starvation does decrease, though 
slowly, the sugar of the blood ; and, on the other hand, Kiilz has shown that 
even starvation for twenty days does not fully free either liver or muscles from 
glycogen. Seegen, however, is determined to adhere to his opinion that gly¬ 
cogen does not form glucose, but fat, and that the liver for purposes of vital 
energy produces glucose from fat and proteids. At the same time that Seegen 
denies the formation of glucose from the glycogen of the liver he accepts such 
a formation from the glycogen of the muscles. This surely appears a rather 
far-fetched theory, and the presumed facts on which it is based have not been 
established, nor would they necessarily lead to Seegen’s conclusions even if 
they were so; but, according to the strongest evidence, some of them are false. 
Naturalists will not, without convincing proofs, believe that nature should form 
exclusively fat from carbohydrates, and at the same time and in the same 
organ should form carbohydrates from fat; and even those who believe that 
fat may form glucose under certain circumstances are far from accepting 
Seegen’s views, which now, like Pavy’s, may be considered to be a matter of 
history. 

We now have acquired a right to consider the liver as the main 
sugar-producing organ of the body, and to look upon the sugar of 
the liver, which is identical with the sugar of the blood, as derived 
from the glycogen. We have seen that the sugar of the blood 
usually is most abundant in the vessels leaving the liver, and that 
it decreases and disappears if the liver is cut off from the circula¬ 
tion. We have seen also that, when the sugar increases in portions 
of liver, there is a corresponding decrease in glycogen. This fact 
may be demonstrated experimentally even during life by irritation 
of the celiac plexus or the sympathetic nerves of the liver, which 
produces an immediate increase in the amount of sugar with a 
corresponding decrease in the amount of glycogen (Chauveau, 
Cavazzani and Butte, Morat and Dufour). Marcuse has lately 
shown that the diabetes that is constantly caused also in frogs by 
extirpation of the pancreas is prevented by previous extirpation of 
the liver. Finally, we know that phloridzin, which causes the sugar 
of the blood to pass into the urine without hyperglycemia in con¬ 
sequence of changes in the kidneys, and causes a constant and rapid 
reproduction of glucose, decreases the glycogen, and that diabetes 
following the extirpation of the pancreas, with the consequent enor¬ 
mous losses of glucose, has the same effect. 


184 


DIABETES MELLITUS AND GLYCOSURIA. 


Generally, glycogen is believed to represent fixed, stored-up 
potential energy, which, whenever it is found, may be changed into 
glucose, representing potential energy in solution ready to be trans¬ 
formed into vital force. 

So far, so good ; but what about the important questions that 
next present themselves ? 

Does all transformation into vital force necessarily pass through 
the molecular structure of glucose, or may proteids and fat be 
used unchanged for this purpose ? 

Can glucose be formed from proteids anywhere else than in the 
liver ? 

Can glucose be formed at all from fat ? 

Can carbohydrates and, perhaps, fat contribute to a possible syn¬ 
thetic formation of proteids ? 

Where and how are the molecules of fat attacked and disinte¬ 
grated ? 

It appears to me, unfortunately unable to form an opinion on 
these subjects, but, from the researches of others, that we can at 
present not give much more definitive answers to these questions 
than we could in the beginning of the last decad of the nineteenth 
century. 

Chauveau has recently formulated his own conclusions from 
extensive researches on the transformation of force within the or¬ 
ganism. These conclusions, in a somewhat abbreviated form, are 
as follows : 

1. All vital force within the organism is produced by oxidation. 

2. The potential energy is always in the ultimate stage repre¬ 
sented by carbohydrates. 

3. During starvation carbohydrates are constantly formed also 
by a rudimentary oxidation of fats. 

4. Oxidation of proteids never directly contributes to the pro¬ 
duction of vital force ; or, in other words, mechanical work does 
not increase the amount of nitrogen in the urine. 

Unfortunately, there are still various opinions with regard to 
each of these conclusions. Munk, Zuntz, and others think it still 
doubtful that all vital force is produced by oxidation. We know, 
especially from the researches of Zuntz, that mechanical work in 
some way may be sustained by fat and by proteids, as well as by 


METABOLISM AND NUTRITIVE NEEDS. 1 8 5 

carbohydrates, and Newton Heyneman’s experiments prove also, 
by the figures of the respiratory quotient, that the kind of food 
chiefly ingested, be it proteids, fat, or carbohydrates, is also chiefly 
used for the production of mechanical force. 

The power of the organism to produce carbohydrates from fats is 
exceedingly doubtful. Something maybe said in favor of the exist¬ 
ence of such a power, but it seems to me that still much more may 
be said against it. The chief reason—apart from the much opposed 
results of Seegen’s experiments—for believing in the formation 
of glycogen or glucose from fats depends on the highly uncertain 
theory that muscles can not use fats as fuel for their work. It has 
been demonstrated that with a scanty supply of carbohydrates the 
quantity of proteids and carbohydrates consumed does not always 
cover the expense of the mechanical work performed. The for¬ 
mation of carbohydrates from fats in vegetable cells constitutes 
absolutely no reason for admitting such a formation in animal cells. 
Any one who has at all occupied himself with the physiology of 
plants knows what an enormous metabolic difference there is be¬ 
tween animals and plants. The clinician, who constantly finds that 
he may increase the butter in the food of his diabetic patients to 
any ingestible quantity in any stage of diabetes and under any diet, 
without any perceptible increase of the amount of glucose in the 
urine, will have strong doubts as to the formation of carbohydrates 
from fats even with a deficient supply of carbohydrates ; and, how¬ 
ever much it may be repeated from some quarters that the sugar 
of the blood remains at par during feeding with fats alone, Seegen’s* 
own figures show that the sugar of the blood, after having dimin¬ 
ished during starvation continues to do so during subsequent feeding 
exclusively on fats. Von Mering, Moritz and Praussnitz, Cremer 
and Ritter, and now (1898) Kumagawa and Miura alike consider 
that during phloridzin-poisoning, with its enormous loss of glucose, 
fats do not give rise to carbohydrates. 

Chauveau has been led to his conclusions as to the ability of the organism 
to produce carbohydrates from fats chiefly by his own and by Regnault’s and 


* Among authorities now living, so far as I know, only Seegen, v. Noorden, Bunge, 
Chauveau and Kaufmann, and Weiss accept the formation of carbohydrates from fats in 
man. 

13 



186 


DIABETES MELLITUS AND GLYCOSURIA. 


Reiset’s investigations on the marmot. This animal, when subjected to star¬ 
vation in summer, dies after the loss of between 95 per cent, and 97 per cent, 
of its fat, and then has scarcely any carbohydrate at all left in liver, muscles, 
or blood. After hibernation the marmot has used up its fat, but the blood still 
contains glucose and the liver and muscles contain glycogen. Chauveau 
asks how this could be, after such a time of continued abstinence from food, 
with considerable expenditure for heat and circulation, if the carbohydrates 
(glycogen and glucose) had not been formed from fat. Then Regnault and 
Reiset had observed that the marmot may, during its sleep in hibernation, 
increase in weight, and that it consumes considerably more oxygen than it 
expires in carbonic acid, and Chauveau thinks that the fat has been changed 
into glucose by oxidation according to the following equation : 

2 ^57^no^6 T 6 7 0 2 = i 6C 6 H 12 0 6 -f- i8C0 2 I 4 H 2 0 . 

Stearin. Glucose. Carbonic Water. 

Acid. 

The question whether proteids directly produce vital force is not 
to be answered at present. Voit, Brietske, Fick and Wislicenus, 
and others found no increase in the nitrogen of the urine after 
mechanical work. Pavy, Flint, Parkes, Argutinsky, Oppenheim, 
and others arrived at opposite results, and Zuntz, too, after his 
beautiful researches, has formed the opinion that proteids (and fats) 
may directly contribute to the formation of vital force. 

Finally, it is not impossible that a part of the proteids so utilized 
is derived from carbohydrates. Pfliiger, Schenk, and others admit 
a synthetic formation of proteids, as a station on the way to the 
final production of vital force, to which formation carbohydrates 
may contribute part of the nonnitrogenous constituents. So long 
as we do not know more than we do at present of the fate of the 
fats, we can not absolutely deny its participation in such a synthesis 
of proteids. 

Until further information is forthcoming it must be admitted that 
proteids may form proteids, fats, and carbohydrates, that carbo¬ 
hydrates may form carbohydrates and fats, but that fats are not 
positively known to form anything but fat. On the other hand, we 
have no right to deny positively the formation under some circum¬ 
stances of carbohydrates from fat; still less have we a right to 
deny the synthesis of proteids, in which both carbohydrates and 
fats may participate. 

The sugar of the blood is proved to be glucose, and is found in 
the serum. 


METABOLISM AND NUTRITIVE NEEDS. 


1S7 


The quantity of sugar in the blood varies normally from 
O. IO to 0.15 per cent., and it may, perhaps, sometimes slightly 
exceed these limits in either direction. The veins contain some¬ 
what less than the collateral arteries. The portal vein, except after 
the ingestion of large amounts of carbohydrate, contains less and 
the hepatic veins contain more than do other vascular areas. 
Unlike the glycogen of the liver, which varies enormously under 
different dietetic conditions, the amount of sugar in the blood nor¬ 
mally undergoes but comparatively slight variations. It increases 
somewhat after the ingestion of large amounts of carbohydrate 
(Claude Bernard, v. Mering) and after copious hemorrhage (Edel, 
Schenk), and decreases during continued starvation (Bernard, 
Bock and Hoffmann, Otto, Seegen, Chauveau), during the febrile 
state, after extirpation of the liver, and as a result of poisoning 
with phloridzin. The quantity of sugar in the blood is about 
half of the quantity of fibrin, and the amount is not small consid¬ 
ering that the sugar is being constantly produced and constantly 
consumed. Seegen calculates that a human being produces and 
consumes about 10 grams of glucose per kilogram of bodily 
weight in twenty-four hours. A German, Anglo-Saxon, or Scan¬ 
dinavian of ordinary size thus manufactures and uses up between 
700 and 800 grams. 

The sugar of the blood is consumed in the different tissues of 
the organism, but chiefly in the muscles ; and by its oxidation into 
carbonic acid and water it forms the organism’s largest, but prob¬ 
ably not its only, source of vital power. 

The sugar of the blood causes reduction of copper- and bismuth-solutions; 
undergoes fermentation, with the generation of alcohol, carbonic acid, etc.; 
forms with potassium a combination, out of which it may be driven by car¬ 
bonic acid (Seegen, Ludwig, Abeles); deflects the ray of polarized light to the 
right (Ewald); and yields glycosazone with phenyl-hydrazin-chlorate and 
sodium acetate (Pickhardt). Thus, there is no doubt that it is glucose. To 
this rule there may, however, be rare exceptions; it seems probable that in 
cases in which the sugar in the urine is another saccharid— e. g. t levulose— 
the sugar of the blood is also constituted by this saccharid. 

Otto proved the sugar of the blood to be contained in the serum by intro¬ 
ducing in Hoppe-Seyler’s equation for the valuation of blood-corpuscles from 
the quantity of plasma and fibrin (in two cases) the figures of the sugar instead 
of the figures of the fibrin, arriving at nearly the same figures as Hoppe- 
Seyler’s equation gave. Calculating with the aid of Hoppe-Seyler’s equation, 


188 


DIABETES MELLITUS AND GLYCOSURIA. 


he found in one case 64.65 per cent, of plasma and 35.35 per cent, of red 
blood-corpuscles ; and with his own equation he found the corresponding 
figures to be 64.29 and 35.71. In a second case the analogous figures were 
67.88 and 32.12, and 67.96 and 32.04. The figures representing fibrin and 
sugar were as follows : 


Cases. 

Blood. 

Plasma. 

Fibrin. 

Sugar. 

Fibrin. 

Sugar. 

I,. 

0.205 percent. 

0.116 per cent. 

0.317 per cent. 

0.182 per cent. 

2,. 

0.311 “ 

0.123 “ 

0.458 

0.181 “ 


Naunyn states the normal quantity of sugar in the blood as about 0.1 per cent. 
—rather somewhat below (from 0.08 to 0.09) than above this figure ; Bernard 
found between 0.09 and 0.117 per cent.; Seegen, between 0.12 and 0.19, and 
as an average in ten cases, nearly 0.17 per cent.; Otto, nearly 0.12 per cent.; 
v. Mering (in the serum), between 0.13 and 0.14 per cent. ; Frerichs, between 
0.12 and 0.30 (!!!) per cent. All of these figures refer to man. In the rab¬ 
bit Otto found between 0.09 and 0.11 per cent.; Barral, in the dog, between 
0.08 and 0.17 per cent. ; Otto, in the dog, o.n per cent. The highest of these 
figures include not only the sugar, but all reducing-substances in the blood 
(kreatinin, uric acid, etc.), and thus represent too high a value for the glucose. 
Otto corrected this error, which, besides, shows a wrong relation between the 
quantity of sugar in the arteries and that in the veins, the reducing, nonsac¬ 
charine substances being present in greater quantity in the veins than in the 
arteries. Otto found in the dog, in blood from the femoral artery, a reduction 
before fermentation of 0.160 per cent., and after fermentation of 0.034 per cent., 
the amount of glucose thus equaling 0.126 per cent.; in blood from the femoral 
vein of the same dog a reduction before fermentation of 0.158 per cent., and 
after fermentation of 0.039 per cent., the amount of glucose thus equaling 
0.119 per cent. (The blood was taken simultaneously from both vessels.) 
After hemorrhage the reduction is increased. Otto considered this to be an 
effect of the increase of nonsaccharine reducing-substances. Bernard had 
mentioned this increase as due to the presence of an increased amount of 
glucose, and Schenk,* in opposition to Otto, maintains that the whole increase 
is due to the presence of glucose. 

The excess of glucose in the arteries over that in the veins is small; accord¬ 
ing to Otto, the proportion is 12 : 11 ; according to Barral, 100 : 92.7. As alreadv 
mentioned, the hepatic veins generally contain most, and the portal vein least 
sugar of all vessels. The great difference, however, that has so often been 
found is in part the effect of a marked increase in the production of sugar 
in the liver from nervous causes during the experiment. Mosse, who arranged 
his experiments with a view to the elimination of this influence, found only 


*“ Pfliiger’s Archiv,” 1894. 
























METABOLISM AND NUTRITIVE NEEDS. 


189 


0.107 per cent, of glucose in the hepatic veins; the portal vein rarely contains 
less than 0.08 or 0.09 per cent. After the ingestion of large amounts of carbo¬ 
hydrate the portal vein may contain as much as 0.4 per cent., and much more 
than the hepatic veins (v. Mering). 

The accompanying table, showing the results of Seegen’s experiments, illus¬ 
trates the influence of diet on the amount of glycogen in the liver and the 
amount of glucose in the blood. The figures representing the amount of 
glucose in the hepatic veins probably are much too high, from the influence of 
the experiment on the nerves ; and all the figures relating to glucose in reality 
represent both glucose and other reducing-substances. Nevertheless, I con¬ 
sider the relations of this conscientious experimenter’s figures to be of great 
value. The observations were made upon dogs that had been subjected to 
starvation for eight days, and were then fed exclusively on one of the several 
kinds of food named. I would call attention to the most important fact that 
both glucose and glycogen reach their lowest figures when the period of pre¬ 
liminary starvation is followed by a period in which the only food is fat. 


Food. 


Glucose. 


Glycogen 

IN 

Liver. 

Carotid. 

Portal Vein. 

Hepatic Vein. 

None,. 


0.147 per cent. 

0.269 P er cent. 

1.67 per cent. 

Fat,. 


0.114 “ 

O.217 “ 

0.93 

Muscle,. 

0.155 “ 

0.141 “ 

0.281 “ 

3-7 

Starch, . 


0.147 “ 

0.261 “ 

6.0 “ 

Cane-sugar, .... 
Cane-sugar and dex- 

0.165 “ 

0.186 “ 

0.265 “ 

9.4 

trin,. 

0.176 “ 

0.258 “ 

O.327 “ 

12.0 “ 


Chauveau and Kaufmann, in 1886, brought to light important facts in con¬ 
nection with the consumption of glucose in the muscles. They determined the 
amount of both carbonic acid and glucose in the blood from the masseter 
muscle and from the parotid gland, having previously made a corresponding 
analysis of the blood in the carotid. This artery supplies the muscle and 
the gland with about the same amount of blood, which in both is about three 
times as large during functional activity as during repose. During functional 
activity the muscle consumed about 5 y z times as much glucose as the gland 
and produced about five times as much carbonic acid. The muscle in exercise 
produced about 3 y z times as much carbonic acid as in repose, and also con¬ 
sumed about y/ z times as much glucose. With the gland, the figures during 
functional activity and in repose were as 87 : 60 with regard to the production 
of carbonic acid, and as 90 : 70 with regard to the consumption of glucose. 

Ouinquaud found from 0.12 to 0.15 per cent, of glucose in the femoral vein 
before, but only 0.07 per cent, after strong faradization. 

As soon as the sugar in the blood reaches a certain amount, 
which Claude Bernard found to be about 0.25 per cent, in the dog, 



















I 9 O DIABETES MELLITUS AND GLYCOSURIA. 

it begins to pass over into the urine. Lepine, immediately after the 
beginning of the glycosuria in diabetic dogs (following extirpation 
of the pancreas), found between 0.19 and 0.24 per cent, of glucose 
in the blood. Seegen’s figures indicate that glycosuria in man may 
exist with less glycemia than 0.20 per cent. Still, there seems to 
be a certain interval between the ordinary glycemia, which only 
rarely exceeds o. 15 per cent., and the decided hyperglycemia, in 
connection with which glycosuria begins. Thus, we find glyco¬ 
suria often absent in states that bring about hyperglycemia— e. 
asphyxia. Carcinoma is usually (Freund), though not constantly 
(Matrai), attended with hyperglycemia, but is often found without 
glycosuria. In cases of simple glycosuria only the highest degrees 
of glycemia give rise to glycosuria, which appears for only a short 
part of the day some time after meals. In cases of diabetes there 
is always hyperglycemia in the severe and often in the light stage. 
It rarely exceeds 0.4 per cent., but much higher figures are occa¬ 
sionally reached. Pavy found 0.57 and Hoppe-Seyler 0.9 per 
cent, of glucose in the blood. Investigations have proved that 
the glycosuria bears no fixed relation to hyperglycemia (Seegen, 
Lepine, and others). Seegen found 3.8 per cent, of sugar in the 
urine and 0.182 per cent, in the blood ; and afterward, in the same 
(mild) case, 0.6 per cent, in the urine and o. 181 per cent, in the 
blood. In a severe case during the observance of a strict diet he 
found 0.6 per cent, in the urine and 0.19 per cent, in the blood. 
We thus see that the hyperglycemia, even with considerable gly¬ 
cosuria, may be quite moderate. Still, the hyperglycemia consti¬ 
tutes the real “ nocens ”—the sugar in the urine, which alone we 
are generally able to observe, is of small account. A moderate 
hyperglycemia, however, is certainly capable of only a moderate 
noxious influence. We are terrified on finding a glycosuria of 3.8 
per cent, in a patient, but should be much less alarmed if told at 
the same time that it resulted from a hyperglycemia of only 0.18 
per cent. Every one understands at once that if it is normal for 
the blood to contain 0.12 per cent., or even 0.15 per cent, of glu¬ 
cose, it does not constitute a very great danger for it to contain 
0.18 per cent, of glucose. 

I now arrive at that much-discussed question whether hypergly¬ 
cemia and glycosuria— i. e. } diabetes mellitus—arise from an in- 


METABOLISM AND NUTRITIVE NEEDS. I9I 

creased production or from a decreased consumption of sugar, or 
from both of these causes. 

The first essential difference in metabolism between the normal 
and the diabetic individual is met with in the liver, which exhibits 
a decreased capability of storing glycogen. The opinion is held 
by many that this deficiency of forming glycogen—which may 
afterward be used for producing fat, or, in case of need, may be left 
to the blood as glucose—is the immediate cause of diabetes. The 
liver is incapable either of keeping the formed glycogen in that 
state or of transforming enough of the glucose derived from the 
food into glycogen, and thus it produces or permits too large quan¬ 
tities of glucose to escape into the circulation. Claude Bernard 
believed the increased production of sugar in the liver to be a result 
of hyperemia and of the action of the diastatic ferment in the blood 
in attacking the glycogen too vigorously—“ /’augmentation de 
rapidite de la circulation du foie accroit la glycemie ” 

Others— e. g., Zimmer—sought to find the root of the evil in the 
muscles and in an impaired consumption of the sugar of the blood. 
When in these latter days it was discovered that extirpation of the 
pancreas causes diabetes, and that extirpation of the thyroid gland 
causes myxedema, Brown-Sequard formulated the theory of an 
“ internal ” secretion of the glands in addition to that which had 
hitherto alone been observed. The profession, as already men¬ 
tioned, for a large part adopted the view that the pancreas, through 
an internal secretion, sends into the blood some substance necessary 
to the combustion and the utilization of the sugar. 

Claude Bernard was familiar with this “ glycolytic ferment,” or, 
as Nommes calls it, the “ glycolysine.” It is this ferment that 
drives the sugar out of the extravasated blood in about twenty- 
four hours. Bernard used acetic acid, carbolic acid, or sodium 
sulphate to prevent or retard this disappearance. Lepine has pro¬ 
posed as a unit of glycolytic power the relative quantity of sugar 
that disappears from the blood in one hour at a temperature of 38° 
C. (100.4° F.). The normal unit is about twenty per cent, of the 
whole amount. According to Lepine and Barral, the glycolytic 
power—which seems to be subject to great variations within the 
normal—is quite low at a temperature of 15 0 C. (66° F.), but it 
increases then for a while with the higher temperature, and is very 


I 92 DIABETES MELLITUS AND GLYCOSURIA. 

strong at 40° C. (104° F.). At 52° C. (125.6° F.) it suddenly 
decreases, and is annihilated at 54 0 C. (129.2 0 F.). Lepine and 
his disciples have made extensive researches upon the glycolytic 
ferment, which, according to that observer, is partly, but not ex¬ 
clusively, formed in the pancreas, and is delivered to the blood and 
the lymph ; it is, further, chiefly, but not exclusively, fixed in the 
white blood-corpuscles. Spitzer found the glycolysis effected both 
by the red and the white blood-corpuscles. The process is one of 
oxidation, oxygen being taken up and carbonic acid produced (Kraus, 
Spitzer). Barral found that oxygen and ozone slightly increase, while 
rarefied air, carbonic acid, and carbon monoxid diminish the glyco¬ 
lytic power. Acidity also lessens and finally annihilates the glyco¬ 
lytic power. This is also the effect of antipyrin (Lepine and Barral, 
Brouardel and Loye), of sodium carbonate, of morphin, and of vale¬ 
rian (Butte). Colenbrander made the observation that the glyco¬ 
lysis is destroyed by the extract of leeches. Curare augments it 
somewhat (Butte). The glycolysis is about as energetic after as 
before defibrination (Dastre). 

Lepine considers that there is a certain alternation between the 
“internal” secretion (of the glycolytic ferment) and the external 
secretion (of the pancreatic juice) in the pancreas. By irritation of 
the peripheral stump of the pneumogastric nerve Lepine caused 
increased secretion of pancreatic juice, and found that at the same 
time the blood from the pancreatic vein had almost entirely lost 
its glycolytic power, which afterward returned, when the external 
secretion had moderated. 

After ligation of the pancreatic duct the glycolytic ferment in the 
blood is increased, probably as a result of pressure on the glandu¬ 
lar cells in consequence of stasis. 

In cases of diabetes the glycolytic ferment in the blood is 
markedly diminished, according to Lepine and many others ; there¬ 
fore less sugar is consumed in the tissues, and hyperglycemia, with 
its various consequences— i. e., diabetes—arises. 

Lepine and Metroz * found that in normal blood—at 3 y° C. 
(98.6° F.)—the sugar had decreased, as a result of glycolysis, 
from 0.13 per cent, to o. 10 per cent.; i. e., the blood had lost 


* “ Corapt. Rend.,” 1893. 



METABOLISM AND NUTRITIVE NEEDS. 1 93 

23 per cent, of its sugar. In diabetic blood under the same 
circumstances the glycolysis may bring down the sugar from 
0.32 to 0.29 per cent., and the loss amounts to less than io per 
cent. Not only the relative, but also the absolute, loss of sugar is 
smaller in diabetic than in normal blood ; but relative loss is the 
one to be taken into consideration. Lepine and Metroz have found 
that a liter of normal blood customarily loses in the course of an 
hour about 0.20 gram of sugar, but that an addition of glucose to 
this same blood may cause the loss, under otherwise the same cir¬ 
cumstances, to amount to 0.60 gram. 

Lepine observed chyle from the thoracic duct of a normal dog 
injected in the veins of a diabetic dog diminish for a short time the 
glycosuria. Lepine and Barral, by adding such chyle to a solution 
of glucose in water, also produced “glycolysis,” with loss of glu¬ 
cose. They also found the normal difference between arterial and 
venous blood decreased in diabetes. By driving the blood through 
the extirpated kidney of a dog in Jacoby’s apparatus they proved 
that loss of sugar takes place in the tissues independently of ner¬ 
vous influences.* For the details of the extensive researches of 
Lepine and his disciples I must refer to his own treatises. 

Hedon also, by a series of investigations, has tried to establish a 
defective glycolysis in cases of diabetes and to exclude an increased 
production of sugar in the liver. He maintains that on separating 
the liver from the circulation the sugar disappears (by glycolysis) 
from normal, but not from diabetic, blood. Minkowski submits that 
this last fact may depend upon an abnormal transformation into 
glucose of the glycogen of the muscles. For other results of 
Hedon’s researches also I must refer to the original communica¬ 
tions. 

Several experimenters, and especially Minkowski, have come to 
other conclusions than those of Lepine. Minkowski found the 
glycolysis in the blood of a diabetic dog to be quite normal, and he 
was not able to reduce the glycosuria by injections of glycolytic 
ferment or of pancreatic extract; he points out that the experiments 
with Jacoby’s apparatus do not exclude postmortem changes— 
Qui vivra y verra ! 


* Barral, “ Sucre du Sang,” Paris, 1890. 




194 


DIABETES MELLITUS AND GLYCOSURIA. 


Lepine also mentions a “ pouvoir sacchariferant ” of the blood. 
While the “ pouvoir glycolytique ” ceases at 54 0 C. (129.2° F.), 
the saccharification, which is effected in the serum, is at its best at 
from 56° to 58° C. (132.8° to 136.4° F.), and gives rise to the pro¬ 
duction of about one gram of sugar to the kilogram of blood. The 
material for this production of glucose is, according to Lepine ( vide 
Seegen), left by peptones. The “ pouvoir sacchariferant ,” like the 
“ poiivoir glycolytique ,” is increased by acute, but reduced by slow, 
asphyxia. 

Lepine, while laying the greatest stress on reduced “ glycolysis ” 
and diminished consumption of sugar as a cause of diabetes, pru¬ 
dently does not deny an increased production of glucose as an addi¬ 
tional cause. It is interesting to note Kaufmann’s plea * for the 
view at which he and Chauveau have arrived as a result of numerous 
experiments. The production of sugar is, according to Kaufmann, 
like the oxidation in the lungs, a regulative function of one organ. 
The consumption of sugar, on the other hand, is a common quality 
of the different tissues, which consume sugar in order to be able to 
perform their functions, but which do not perform their functions 
for the purpose of consuming sugar. When a deviation from the 
normal takes place, it is more reasonable to look for the cause in the 
organ among whose functions is the production and distribution of 
sugar— i. e., the liver—than in those organs that have only indirectly 
anything to do with the sugar. In hibernating animals, in spite of 
their comparatively profound muscular repose, one does not find 
hyperglycemia but hypoglycemia, and only when they return to 
muscular activity does the sugar in the blood reach its full amount. 
In this instance production is seen to depend on consumption. 
Chauveau and Kaufmann, in 1893, demonstrated the fact that the 
sugar increases in organs, especially in muscles, when they are 
occupied in their functions. By administering large amounts of 
glucose or by injections of glucose into the portal vein one may 
induce a glycosuria that manifestly has nothing to do with 
diminished consumption, but with the overstraining of the liver’s 
capability of transforming and storing glucose in the form of 
glycogen. This capability is reduced in cirrhosis of the liver ; this 


* “ Sem. Med.,” January 16, 1895. 




METABOLISM AND NUTRITIVE NEEDS. 


195 


is the cause of the frequency of glycosuria in connection with that 
disease. Kaufmann further calls attention to Dastre’s view that in 
cases of asphyctic glycosuria the asphyctic blood causes an abnor¬ 
mally large production of sugar in the liver by stimulating the 
organ to increased activity. In the course of glycosuria due to 
other poisons (curare, morphin, and anesthetics in general) there is 
certainly a reduction in oxidation and in consumption ; but the 
glycosuria is not caused by this, being often developed during the 
stage of excitement, before the decrease of oxidation and consump¬ 
tion ; under these conditions also the glycosuria results from 
increased production. After Bernard’s puncture, with the develop¬ 
ment of glycosuria the consumption of sugar is normal (Chauveau). 
In the course of glycosuria from irritation of peripheral nerves the 
animals are much excited and consumption is increased. After 
section of the spinal cord between the last cervical and the first 
dorsal vertebra Bernard found (after a transitory hyperglycemia 
from the operation per se), in spite of the lameness and reduced 
consumption, no hyperglycemia, but a decided hypoglycemia. The 
lowered temperature in cases of severe diabetes does not depend on 
the diabetes, but on the marasmus. 

Chauveau and Kaufmann * accept a combined activity of the liver 
and the pancreas for the regulation of the glucose—economy of 
the organism, each organ having an inhibitory and a stimulating 
nervous center influencing its secretion. The medulla oblongata 
contains a stimulating center for the pancreas and an inhibitory 
center for the liver, f When the stimulating center for the pan¬ 
creas becomes active, the internal secretion of the pancreas increases 
and stimulates the inhibitory center for the liver; this secretion has 
at the same time an inhibitory influence on the stimulating center 
for the liver located in the cervical part of the spinal cord above the 
fourth cervical vertebra. The production of glucose in the liver 
is thus diminished by a twofold influence. 

Chauveau and Kaufmann, besides, accept an inhibitory influence 


* “ Comptes rend., ” 1893-1897. 

f The inhibitory center for the liver transmits its impulses through the “ rami com- 
municantes ” of the first four pairs of cervical nerves. Its stimulating center transmits 
its impulses through the “ rami communicantes ” below the first four pairs down to the 
sixth dorsal vertebra. 



I96 DIABETES MELLITUS AND GLYCOSURIA. 

from the stimulating center for the pancreas on the whole general 
metabolism—the “histolysis” in the tissues.”* This histolysis, 
they further state, results in the bringing to the blood certain sub¬ 
stances, which are again carried to the liver and there transformed 
into glycogen and glucose. The same influence of the pancreas 
that otherwise inhibits the production of glucose in the liver thus 
also diminishes its supply of carbohydrates. 

A section through the spinal cord between the atlas and the 
occipital bone separates the liver from its inhibitory centers and 
delivers its stimulating center in the upper cervical cord from its 
antagonist; at the same time it separates the pancreas from its 
stimulating center and cuts off communication between the cere¬ 
bral centers and the sympathetic nervous system (inferior cervical 
ganglion), which executes the impulses transmitted from the cere¬ 
bral centers. The internal secretion of the pancreas does not cease, 
but it is considerably diminished, and the effect of the operation 
is a hyperemia, quite distinct from, and less pronounced than 
that which follows total extirpation of the pancreas. Bernard’s 
puncture on the floor of the fourth ventricle has the same effect, in 
consequence—according to Chauveau and Kaufmann—not of stim¬ 
ulation, but of a paralyzing effect on the nervous center of excitation 
for the internal secretion of the pancreas, f 

Section through the cord below (or behind) the fourth cervical 
vertebra, and between this and the sixth thoracic vertebra, leaves the 
communication between the cerebral stimulating center for the pan¬ 
creas and the cerebral inhibitory center for the liver, but cuts off 
the stimulating center for the liver, and the effect is not hypergly¬ 
cemia, but distinct hypoglycemia. Sections below the sixth tho¬ 
racic vertebra have no influence on the amount' of sugar of the 
blood. 

If the pancreas is extirpated after section of the cord between 


* I fear that it is impossible to bring this part of Chauveau’s and Kaufmann’s theories 
in accordance with the established facts concerning the metabolism of diabetic patients. 

f Kaufmann later, after cutting all the nerves of the liver, found that hyperglycemia 
still follows Bernard’s puncture, and he therefore also accepts a direct influence, outside 
of the nervous system, of the internal secretion of the pancreas on the liver. This inter¬ 
nal secretion and its inhibitory influence on the liver are diminished by the paralyzing 
influence of the puncture on the stimulating center for the pancreas. 



METABOLISM AND NUTRITIVE NEEDS. 197 

the fourth cervical and the sixth thoracic vertebra, diabetes does not 

to 

develop, but the hypoglycemia continues, the stimulating center for 
the formation of glucose in the liver being cut off. If, however, the 
pancreas is first extirpated, and the same section is made after the 
beginning of the diabetes, hyperglycemia and glycosuria continue. 
Chauveau and Kaufmann explain this by a certain autonomy on the 
part of the sympathetic centers in the abdominal cavity, which con¬ 
tinue to exercise stimulating functions after these have once been 
assumed. 

For the same reason hypoglycemia continues if the cord is first 
severed between the fourth cervical and the sixth thoracic vertebra 
and section of the medulla oblongata above the atlas is made after¬ 
ward. For the same reason hyperglycemia continues after section 
of the medulla above the atlas, if later the cord is severed between 
the fourth cervical and the sixth thoracic vertebra. 

After publication of the foregoing results Kaufmann * came to 
the conclusion, from further experiments, that Lepine’s observations 
concerning diminished “glycolysis” on the part of the blood after 
total extirpation of the pancreas are correct. Kaufmann, too, has 
found (in dogs) diabetic after such extirpation, a reduction of “ gly¬ 
colysis ” from i to 0.77, or even to 0.68, and a normal or even 
slightly decreased production of sugar. He maintains his pre¬ 
viously expressed views, so far as they are not directly affected by 
Lepine’s and his own observations on the effect of extirpation of 
the pancreas on glycolysis. He accepts two secretions on the 
part of the pancreas : one, the well-known external secretion, 
among whose functions is the production of glucose from the in¬ 
gested carbohydrates ; and the other, the recently discovered inter¬ 
nal secretion, among whose functions is the production both of a 
glycolytic ferment and of a substance possessing an inhibitory influ¬ 
ence upon the production of glucose in the liver. Kaufmann thus 
adopts at present the view that will probably in the future be uni¬ 
versally accepted. He believes that diabetes mellitus may arise 
from an increased production of glucose in the liver or from a de¬ 
creased consumption of glucose in the tissues, especially in the 
muscles, or from both of these causes in combination. 


* “ Comptes rend. hebd. Soc. de Biologie, ” 1896. 




198 


DIABETES MELLITUS AND GLYCOSURIA. 


The results of Chauveau’s and of Kaufmann’s experiments tend 
to make a pathologic unit of all varieties of decreased power of 
assimilating carbohydrates. The hypothesis of the two distin¬ 
guished French physiologists must, however, be confirmed by a 
vast amount of experimental work before anything can be con¬ 
sidered settled. For the details of Kaufmann’s numerous and 
laborious experiments I must refer to his own works. 

The clinician certainly sees more manifestly the increased pro¬ 
duction than the decreased consumption of glucose in cases of 
diabetes. A child of 20 kilograms bodily weight requires 800 calo¬ 
ries in twenty-four hours. A diabetic child of equal weight may pro¬ 
duce one kilogram of glucose, representing 3692 calories, in the same 
time, or so enormously much more vital force than is needed or 
can be consumed that such a production under normal conditions is 
not possible. 

As long as we know so little of the laws governing the activity 
of the pancreas and of the liver, or are uncertain with regard to the 
details of the regulatory nervous influence ; as long as the formation 
of carbohydrates from fats is a mystery and the conditions for the 
formation of fats from carbohydrates are unknown ; as long as the 
molecular conditions necessary for the ultimate oxidation are not 
clearer than they are at present, so long shall we, even if we accept 
recent views on the increased production of sugar and on decreased 
“glycolysis” in cases of diabetes, be unable to form any detailed 
or clear opinions on the immediate cause or causes of diabetes, and 
we shall do well to abstain from too much speculation on the sub¬ 
ject and to wait for further conclusions until experimental pathology 
has provided us with the necessary amount of established facts. 

The normal human being after ingestion of carbohydrates other 
than glucose excretes no glucose in determinable quantities in the 
urine. This fact was first proved by Worm-Muller, and I have re¬ 
peatedly verified the correctness of the observation so far as starch, 
cane-sugar, and levulose are concerned. After the ingestion of 
enormous amounts of rice by healthy individuals the urine causes 
no reduction that can be removed by fermentation. My own 
experience has been only with isolated instances in which large 
amounts of carbohydrate have been taken. But healthy Chinese, 
who live almost exclusively on rice, exhibit no glycosuria. After 


METABOLISM AND NUTRITIVE NEEDS. 1 99 

the ingestion of large amounts of the different disaccharids or 
monosaccharids, a comparatively insignificant part of the ingested 
saccharid appears in the urine in unchanged form. My own 
numerous experiments have yielded in all essential respects the 
same results as Worm-Muller’s. After the ingestion of 250 grams 
of cane-sugar, Worm-Muller found 1.81 grams of cane-sugar in the 
urine ; after the ingestion of 50 grams of cane-sugar, he found o. 1 
gram of the same disaccharid in the urine, but not a trace of glu¬ 
cose. The ingestion of 200 grams of lactose was followed by the 
excretion of 1.68 grams of lactose; 100 grams of lactose by the 
mouth yielded 0.32 gram of lactose in the urine. After the in¬ 
gestion of large amounts of honey, which is a mixture of levulose 
and glucose, Worm-Muller found only glucose in the urine. Levu¬ 
lose, however, obeys the same laws as other saccharids. After 
the ingestion of 150 grams of crystallized levulose by a normal 
individual, I found a small quantity of reducing and fermenting 
substance in the urine ; and by doubling the dose I was able to dem¬ 
onstrate that the urine contained no saccharid other than levulose, 
and to observe the difference in levogyration at different tempera¬ 
tures peculiar to this saccharid. 

Miura has lately observed that the ingestion of large amounts of 
different saccharids by healthy individuals is followed by the ap¬ 
pearance in the urine of small quantities of these saccharids exclu¬ 
sively in unchanged form. Maltose yielded maltosuria ; levulose, 
levulosuria ; lactose, lactosuria. Miura found also that the ingestion 
of even enormous amounts of starch by healthy persons is followed 
by the appearance of no abnormal or unusual substance in the 
urine. 

When taken in large amounts, glucose, like other saccharids, ap¬ 
pears in some degree unchanged in the urine in normal as well as 
in diabetic persons. Normal individuals, however, are usually able 
to assimilate considerable amounts of glucose without exhibiting 
glycosuria. Worm-Muller found, in the urine of a person whom 
he accepted as normal, 0.47 gram of glucose after the ingestion of 
only 50 grams of the same monosaccharid. I am inclined to 
believe that in this experiment Worm-Muller happened to come 
across a person with the common, but decidedly pathologic, weak¬ 
ening of the power of assimilation found especially often in brain- 


200 


DIABETES MELLITUS AND GLYCOSURIA. 


workers with some degree of neurasthenia. A perfectly normal 
person can usually take, on an empty stomach or after a light 
meal, at least ioo grams of glucose without consequent glycosuria. 
To again assure myself of this fact, I had, shortly before this manu¬ 
script left my hands, each of fifteen soldiers in Stockholm take in 
my presence, at io A. m., ioo grams of glucose,* a few hours 
after a light breakfast. Not one of them afterward excreted suffi¬ 
cient glucose in the urine to cause any reaction with Nylander’s solu¬ 
tion of bismuth. Two days afterward I gave 200 grams of glucose 
in water to each of ten soldiers ; neither after this amount was there 
in any case sufficient glucose in the urine to yield a distinct reaction 
with Nylander’s solution after four minutes of boiling. 

In other instances 200 grams, and sometimes, though rarely, 
even 100 grams of glucose cause, in apparently healthy persons, 
some slight glycosuria. 

Moritz mentions that large amounts of cane-sugar cause in normal indi¬ 
viduals an excretion of cane-sugar and of glucose. I maintain that when glucose 
appears in the urine after the ingestion of cane-sugar the individuals in ques¬ 
tion are not normal.f 

De Jong, after some experiments with lactose, came to the conclusion that 
large amounts cause in normal men an excretion of lactose and of a compara¬ 
tively small amount of fermentable saccharid. This is contrary to the obser¬ 
vations of Worm-Muller, Miura, and others, and I doubt that the individual in 
question was normal. 

A large number of observations have taught me to conclude that 
any person who exhibits glycosuria after the ingestion of large 
amounts of rice suffers from a deficient, distinctly pathologic power 


* Five of the soldiers received ioo grams of perfectly pure glucose ; all the others 
were given “ technical ” glucose, which contains some dextrin. The urine was secured 
nearly three hours after the ingestion of the sugar. The excretion of the saccharid is, in the 
large majority of cases, ended, or nearly ended, after that length of time. The diuretic 
influence of large amounts of glucose is often apparent, even when there is no glycosuria. 

f I wish again to call attention to the fact that no conclusions can be drawn with 
regard to the details of metabolism in one species of vertebrates from the results of 
observations made upon another species. Seegen found cane-sugar, glucose, and 
levulose in the urine of dogs after the ingestion of large amounts of cane-sugar, and 
Rubner found cane-sugar and glucose. Budge also found glucose in the urine of dogs 
after the ingestion of large amounts of cane-^ugar, but not in man. As to starch, Hof- 
meister mentions that the ingestion of even enormous amounts causes no glycosuria in 
the normal dog. 



METABOLISM AND NUTRITIVE NEEDS. 


201 


of assimilating carbohydrates. To me, such an individual is either 
distinctly diabetic or in danger of becoming so. The appearance of 
glucose in the urine, together with unchanged cane-sugar, after the 
ingestion of large amounts of cane-sugar is a less serious manifes¬ 
tation, but it is not normal, and it takes place in individuals who will 
daily, under ordinary circumstances, show some glycosuria. The 
smaller the proportion of glucose and the greater that of cane-sugar 
in the urine under such circumstances, the more nearly is the patient 
in a normal condition. There are individuals who may take from 
200 to 300 grams of cane-sugar without excreting determinable 
quantities of glucose,—but only some cane-sugar,—and who still do 
not possess perfectly normal powers of assimilation, but present 
glycosuria up to 0.05 or o. 1 or o. 15 per cent, for a short while after 
every dinner of mixed food. 

In cases of diabetes the ingestion of large amounts of carbohy¬ 
drate, continued for any considerable length of time, always causes 
glycosuria ; and the more pronounced the glycosuria, the more ad¬ 
vanced the glycosuric dystrophy. Generally, no other saccharid is 
then found in the urine than glucose. This is always the case after 
ever so large doses of the polysaccharid starch. But after very 
large amounts of disaccharids, or of other monosaccharids than glu¬ 
cose, there will appear, even in cases of severe diabetes, together 
with a large quantity of glucose, a slight quantity of the ingested 
monosaccharid or disaccharid unchanged. This is also the case in 
dogs diabetic after extirpation of the pancreas. Minkowski found, 
after administration of 100 grams of levulose, 98.3 grams of glucose 
and 2.2 grams of levulose in the urine of such a dog. Administration 
of 200 grams of levulose yielded 105.6 grams of glucose and 15.6 
grams of levulose in the urine. 

The addition of proteids to a certain portion of carbohydrate 
increases the glycosuria in all stages of the glycosuric dystrophy. 
Many persons who are able to take large amounts of saccharids 
without the development of glycosuria, often excrete small quanti¬ 
ties of glucose after rich meals of mixed character; and in cases of 
both light and severe diabetes, a portion of meat given with a cer¬ 
tain amount of carbohydrate increases the resultant glycosuria. 

There is only a gradual difference between the different stages of 
diabetes as to the power of assimilating carbohydrates. All dia- 
14 


202 


DIABETES MELLITUS AND GLYCOSURIA. 


betics have this in common, that they lose a part of the ingested 
and digested carbohydrates during a prolonged, abundant supply 
thereof; on this single symptom is built the whole dystrophic group 
of diabetes mellitus. All cases and stages of diabetes also have this 
in common : that they utilize a part of the ingested and digested 
carbohydrates. For the slight deficiency in the power of assimila¬ 
tion that causes a simple glycosuria, only an insignificant part of the 
ingested carbohydrates again appears in the urine as glucose ; the 
individual may eat 300 grams of starch and excrete one gram of glu¬ 
cose in the twenty-four hours. In a case of mild diabetes the 
patient sometimes may receive sixty grams of starch without ex¬ 
hibiting glycosuria, and after long abstinence from carbohydrates he 
may even take large amounts of cane-sugar without manifesting 
any appreciable degree of glycosuria. Even in the worst cases, 
however, the physician, if he has the courage, in spite of the danger 
of coma, to put his patient on an exclusively animal diet until the 
glycosuria reaches a certain fixed degree for the twenty-four hours, 
will find that the patient, when again allowed a certain quantity of 
starch, will excrete a smaller excess above the former quantity of 
glucose than corresponds to the digested part of the ingested por¬ 
tion of starch. It seems that only after extirpation of the pancreas 
in dogs the power of assimilating carbohydrates may sometimes be 
for a short while completely destroyed (Minkowski); but even in 
these cases a certain amount of starch is usually assimilated.* 
Almost all of the glucose eliminated from the blood in cases of 
diabetes passes into the urine. The saliva, the tears, and the sweat 
are generally free from glucose, though it has sometimes been 
found in these in fractions of one per cent.f It is sometimes found 


* A dog, after extirpation of its pancreas, received 151 grams of starch, of which 64.8 
grams were found in the feces and—not including small quantities possibly lost in the 
intestines by fermentation—86.2 grams were digested. The urine contained 99.2 
grams of glucose and 12.22 grams of nitrogen. The sugar formed from proteids, com¬ 
pared to the nitrogen derived from them, bears a ratio as of 2.8 : I, so that 34.21 grams 
of glucose must have been derived from proteids and 64.99 grams from the ingested 
starch. A considerable part of the starch—of which 54 grams correspond to 60 grams 
of glucose—had manifestly been utilized. 

fToralbi mentions a case of “salivary diabetes” in a hysteric woman, without 
glucose, but with a large amount of oxalates in the urine and one per cent of glucose in the 
saliva. 



METABOLISM AND NUTRITIVE NEEDS. 203 

in serous fluids; from 0.14 to 0.27 per cent, in ascites (Letulle, 
Naunyn), 0.5 per cent, in a pleuritic exudate (Foster), etc. Busse- 
nius found 0.25 per cent, in the sputa. 

The greatest amount of glucose to the kilogram of bodily weight 
that can be taken without the development of glycosuria represents 
what Hofmeister calls the limit of assimilation. This limit varies in 
different patients, and also varies in the same patient at different times. 
All of those influences that are known to cause diabetes or glyco¬ 
suria, of course, lower the limit of assimilation. Excesses and emo¬ 
tions cause glycosuriain normal individuals and increase it in diabet¬ 
ics. Starvation or underfeeding has a bad influence in this direction ; 
this was discovered by Claude Bernard and has been elaborately 
studied by Hofmeister (see Glycosurias). Muscular activity within 
certain limits heightens the limit of assimilation (Bouchardat, Zim¬ 
mer, Kiilz, v. Mering); massage has the same effect (Finkler and 
Brockhaus). Fatigue, however, has a contrary effect, and after long 
marches or after journeys in railway cars the diabetic patient often 
exhibits for several days a lower power of assimilation than under 
ordinary circumstances. Kiilz made an observation which can be 
easily verified—viz., the limit of assimilation is often higher early 
than late in the day. A most important fact (see below) is this : 
that the limit of assimilation is higher after the observance for 
some time of a strict diet and absence of hyperglycemia and gly¬ 
cosuria. Opium, syzygium jambulanum, arsenic, etc., often increase 
the limit of assimilation ; in other cases these drugs have no effect 
whatever. In the course of careful experiments with phenacetin, 
which a physician recommended for increasing the power of assimi¬ 
lation, I was able repeatedly to demonstrate an increased glyco¬ 
suria. Fepine and his disciples have lately given an explanation 
of the fact that the same agent may have quite contrary effects in 
different cases ; it increases both the production and the consump¬ 
tion of glucose, so that its effect on the limit of assimilation de¬ 
pends on the relative state of production and consumption in the 
case. The best remedies, of course, are those that decrease pro¬ 
duction and increase consumption. Alcohol in small doses increases, 
in large doses diminishes, the power of assimilation. Fever decid¬ 
edly increases this power. Finally, the limit of assimilation often 


204 


DIABETES MELLITUS AND GLYCOSURIA. 


slowly sinks, from unknown causes, in consequence of the progres¬ 
sive nature of the glycosuric dystrophy. 

The limit of assimilation varies also in the same individual from 
unknown causes. Worm-Muller gives a striking instance of this : 
V. C., previously mentioned, received 50 grams of glucose before 
breakfast, and excreted 0.47 gram in the urine during the next 
three hours. At another time, under the same circumstances, the 
subject received 100 grams without the development of any glyco¬ 
suria whatever. On a third occasion glycosuria appeared six hours 
after the ingestion of 100 grams of glucose (rare !), and continued for 
three and one-half hours, during which time 1.85 grams of glucose 
were excreted. 

Shortly before death and in advanced marantic states, the gly¬ 
cosuria, ceteris paribus , diminishes—not by reason of an increased 
power of assimilation, but on account of impaired digestion and the 
retardation of all the metabolic processes. The reason why glyco¬ 
suria diminishes in cases of cirrhosis of the kidneys remains to be 
explained. 

Glycosuria following the ingestion of carbohydrates in cases of 
diabetes (and after large amounts of glucose in any person) begins, in 
the enormous majority of cases at least, within the first hour, and 
generally a distinct reaction can be found after half an hour. Bread 
and well-cooked rice seem to cause glycosuria almost as quickly as 
pure glucose. The larger part of the glucose in the urine has often 
been excreted at the end of the first hour ; the curve afterward 
sinks, and after from three to six hours the urine in mild cases is 
again free from glucose. In cases of simple glycosuria the whole 
excretion may not continue for more than an hour, beginning about 
half an hour and often ending an hour and a half after the meal. 
Even with a free diet the mild cases of true diabetes often exhibit, 
some hours after a meal, no glycosuria, and the majority of such 
patients present no glycosuria in the morning before the first meal.. 
This is, therefore, the worst time for testing whether or not an in¬ 
dividual is free from diabetes. 

My patient, T., suffered from simple glycosuria, and with a perfectly free 
diet, including an abundant supply of carbohydrates, excreted about 2 grams 
of glucose in twenty-four hours. Between 9.30 and 10 A. m. he was free from 


METABOLISM AND NUTRITIVE NEEDS. 205 

glycosuria, and drank 300 grams of cane-sugar in 1000 cu. cm. of water, 
excreting afterward as follows : 


At 10.30 A. M. 
At 11 “ 

At 11.30 “ 

At 12 M. 

At 12.30 P. M. 

At 1 “ 

At 1.30 “ 

At 2 “ 

At 2.30 “ ‘ 


130 cu. cm. of urine of I.030 specific gravity and containing 0.2 per 

cent, of sugar. 


95 

66 

66 

1.006 

66 

containing 0.1 per cent, 
of sugar. 

145 

a 

i < 

1.004 

6 6 

containing about 0.07 per 
cent, of sugar. 

36 

a 

u 

1.018 

6 6 

containing 0.15 per cent, 
of sugar. 

24 

< < 

< < 

X 

66 

containing somewhat 
more than 0.1 per cent, of 
sugar. 

21 

6 6 

n 

X 

6 6 

containing less than 0.1 
per cent, of sugar. 

26 

a 

6 6 

X 

66 

containing traces. 

X 

<< 

66 

X 

6 6 

containing faint trace. 

the 

urine 

did not contain as much as 0.01 

per cent, of glucose. 


The figures here given as representing sugar were obtained by polarization, 
and thus refer to the mixture of glucose and cane-sugar in the urine. The 
figures are, besides, all somewhat too low, the levogyration of glycuronic acids 
not being taken into account. 

A medical student, X., rang me up on the telephone, and in a trembling voice 
asked if he might pay me a visit at once; and I, having had several times 
before a similar experience, at once suspected that he had passed glucose in his 
urine. The ingestion of 250 grams of cane-sugar caused him to vomit after 
half an hour. The urine, however, passed a few minutes later contained cane- 
sugar but no glucose, and reduced after, but not before, boiling with some 
sulphuric acid. On the next day X. had better luck, and was able to retain 200 
grams of cane-sugar. About two and a quarter hours afterward he passed 100 
cu. cm. of urine, with a specific gravity of 1.022, and which, before boiling with 
some sulphuric acid, reduced as a solution of glucose of 0.33 per cent.; but 
after “inversion ” (of the excreted cane-sugar) it reduced as a solution of glu¬ 
cose of 0.55 per cent. In the next sample of urine, passed three and a half 
hours after the cane-sugar had been taken, there was no appreciable amount 
either of glucose or of cane-sugar. 

I consider X. more nearly a case of true diabetes than he would be if he had 
passed only cane-sugar and no glucose; but he is better off than he would be 
with greater glycosuria and less saccharosuria. 


Kiilz made it a rule to give the patient the allowed daily quantity 
of starch at one meal, believing that it induced a greater degree of 
glycosuria if given in several portions at different times. The re¬ 
sult, however, depends on circumstances. If the patient’s limit (or 
power) of assimilation is small as compared with the allowed 


206 


DIABETES MELLITUS AND GLYCOSURIA. 


quantity of carbohydrates, this quantity given in several doses may 
occasion the presence of more glucose in the urine than when given 
at one time ; but if the amount allowed is small as compared with 
the power of assimilation, it may induce less glycosuria by being 
given in divided portions than when given at once. This is mani¬ 
fest both from Kiilz’s figures and from mere reasoning as soon as 
the patient can take any quantity of carbohydrates without the de¬ 
velopment of glycosuria. 

Kiilz, in addition to many other services, also rendered that of 
teaching us that different kinds of carbohydrate are assimilated in 
different degree by diabetics. 

Starch induces greater glycosuria than any other article of 
food—greater even than pure glucose. The formula of starch is 
C 6 H 10 O 5 ; that of glucose, C 6 H 1 2 0 6 . By taking up water, starch 
will form glucose : CgH^ 0 O 5 + H 2 0 = C 6 H 12 0 6 . The atomic 
weights being for C = 12, H = 1, and for O = 16, the foregoing 
equation yields 12.6+1 • 10+16.5 + 1 .2+16=12.6+1 . 12 + 
16.6, or 162 + 18 = 180. In other words, 162 grams of starch, 
by taking up 18 grams of water, will form 180 grams of glucose ; or 
9 grams of starch + 1 gram of water will form 10 grams of glucose. 

Cane-sugar is a disaccharid of glucose and levulose. Glucose 
causes marked glycosuria in cases of diabetes ; levulose, much less. 
Thus, cane-sugar causes less marked glycosuria than starch or 
glucose. 

Lactose is easily partly changed by fermentation in the bowel 
into lactic acid, which does not give rise to glycosuria, but often 
causes diarrhea, in consequence of which more than usual of the 
ingested saccharid passes off in the feces. In so far, however, as 
neither the one nor the other occurs, lactose seems to give rise to 
about as marked a degree of glycosuria as does glucose itself. 
Kiilz’s patient, F. S., after the ingestion of 100 grams of glucose, 
excreted 8.9 grams of glucose ; and after 100 grams of lactose, ex¬ 
creted 9 grams of glucose.* Fr. Voit, in a severe case, saw 100 
grams of lactose increase the glycosuria by 49 grams. 


* After five weeks of abstinence from carbohydrates the power of assimilation had 
increased, and ioo grams of lactose gave rise to the excretion of only 4.1 grams of glu¬ 
cose. The glycosuria lasted about three and one-half hours, and the larger part of the 
glucose was excreted within the first hour. 



METABOLISM AND NUTRITIVE NEEDS. 207 

Galactose also gives rise to quite a considerable degree of glyco¬ 
suria. Fr. Voit saw the glycosuria increased by 70 grams in a 
severe case, after the ingestion of 100 grams of galactose. 

Kiilz has published a report stating that the polysaccharid inulin 
and the monosaccharid levulose, which are related chemically in 
the same way as starch and glucose, are completely assimilated by 
diabetics. As soon as the price of levulose made this substance of 
practical value for such a purpose I began to use it in cases of dia¬ 
betes ; in severe cases with pronounced autophagia and loss of 
weight to lessen the daily nutritive deficit, and in mild cases as a 
substitute for cane-sugar. I found levulose of great value in check¬ 
ing the loss of weight in severe cases, and I believe it has a power¬ 
ful effect in warding off the coma for a time. I constantly found 
that levulose increases the glycosuria in severe cases, and that large 
amounts in mild cases also cause glycosuria,* though more of levu¬ 
lose than of other saccharids is assimilated. 

Inulin, a polysaccharid, is found in unusually large quantities in 
the tubers of Helianthus tnberosus, which is sometimes used for 
food in Europe and America, and is known under the name of 
Jerusalem artichokes (topinambour). Boiled with diluted acid it 
yields levulose. It is better assimilated by diabetics than starch, 
though, like levulose, it decidedly increases the glycosuria. 

Inosite does not give rise to glycosuria, even when given in large 
amounts, as in young string-beans (Kiilz). Inosite is, however, not 
a saccharid, and it is not considered as belonging to the carbohy¬ 
drates. Maquenne believes it to be hexahydroxyl-benzol. 

[As is well known, inosite is found in many parts of the human 
organism, and is often present in the urine in conjunction with poly¬ 
uria, with diabetes mellitus or insipidus, and with cirrhosis of the 
kidney. Sometimes glycosuria is succeeded by inosituria. In a 
case of diabetes, Vahl saw the glucose disappear and polyuria 
continue, and observed an excretion of from eighteen to twenty 
grams of inosite in twenty-four hours.] 

Mannite, which is a hexatomic alcohol, causes, according to 


* Gruber, Hale White, Haycroft, Heyse, Klemperer, Minkowski, Palma, and others 
have had a similar experience. In the severe stage Palma found that 100 grams of levu¬ 
lose increased the glycosuria by 60.49 grams. 



208 


DIABETES MELLITUS AND GLYCOSURIA. 


Kiilz, no glycosuria in any stage of diabetes, and normally appears 
in the urine in only small quantities. It may be used by diabetics 
as a mild aperient. 

Other saccharids than glucose are also found in the urine, both 
in normal and in abnormal states. Lactose, as has already been 
mentioned, normally occurs in the urine of mothers during lactation 
and in that of sucking children. Levulose has several times been 
found in cases that have presented otherwise more or less the 
clinical image of diabetes mellitus, and the same may perhaps be 
true of maltose. Laios, found by Leo with glucose in a case of 
severe diabetes, may possibly be a saccharid, but it is as yet very 
little known. 

Gorup-Besanez mentions levulosuria. Zimmer and Czapek have described 
a case of diabetes with as much as 2.2 per cent, of levulose, excreted with 
some glucose. Rohmann and Wolf saw a case with urine that turned the ray 
of polarized light to the right as much as a 1.6 per cent, solution of glucose, 
but reduced as a 4.3 per cent, solution of glucose. It contained in addition 
to glucose a reducing-substance that turned the ray of polarized light to the 
left, was decomposed by fermentation, and was thus in all probability levulose. 
Seegen, in 1884, treated in Carlsbad a case of pure levulosuria. In the follow¬ 
ing year Seegen had left the place and the patient came under my treatment, 
as she did also in 1893 and in 1896. Both Seegen and Kiilz have published 
the case, which clinically is more similar to one of simple glycosuria than to 
one of true diabetes. As it presents a peculiar interest, I briefly describe it 
herewith: 

Mrs. F., a Jewess, born in 1837, knew of nothing else of anamnestic inter¬ 
est than that her mother had suffered from obesity and probably from diabetes, 
the thirst being remarkable during the latter part of life. The patient herself 
was always rheumatic, and since childhood had from time to time been troubled 
by furuncles. She sometimes suffered from dryness of the mouth and from 
increased thirst. At no time, however, had there been distinct polyuria, 
although there was marked pollakiuria. 

The patient was a pronounced neurasthenic with a number of the usual 
symptoms. She suffered from right-sided sciatica. The knee-jerks were some¬ 
what weakened. A sample of the mixed urine for twenty-four hours slightly 
reduced Fehling’s solution. After an abundant dinner, with much carbohy¬ 
drate, there was a deviation to the left of the ray of polarized light of 0.3 0 (with 
Hoppe-Seyler’s instrument), which disappeared for the greater part after fer¬ 
mentation,'when the reduction was almost entirely gone. 

In 1893, nine years afterward, the excretion did not amount to more than 0.3 
per cent, at the utmost, and it was not possible to decide with certainty whether 
or not some glucose was mixed with the levulose. 

In the summer of 1896 the patient again visited Carlsbad, being otherwise 


METABOLISM AND NUTRITIVE NEEDS. 


209 


in about the same state as eleven years before, i. <?., in fairly good health, suf¬ 
fering only from some neurasthenic symptoms and from sciatica on one side. 
The excretion of sugar, however, was larger, and in some samples reached 
almost two per cent. The urine contained no albumin. After removing the sac- 
charid by fermentation I found only a slight and uncertain reducing effect on 
the part of the urine, but a deviation of the ray of polarized light about 0.15 0 
to the left. This undoubtedly arose from combined glycuronic acids, and 
it disappeared after precipitation with ammonia and lead acetate. This devia¬ 
tion taken into consideration, quantitative determinations of the saccharid, very 
carefully performed by methods of polarization and reduction, perfectly agreed 
in results, and I concluded that the urine contained no other saccharid than 
levulose. The quantity of levulose was large enough to enable me to observe 
distinctly the decrease in the deviation of the ray of polarized light at higher 
temperature peculiar^to solutions of this substance. 

Seegen, who had the patient under his care in 1884, then found 3.2 per cent, 
of levulose. Mauthner, who analyzed another specimen of the urine, found 
1.59 per cent, of levulose. The results of polarization and reduction agreed, 
and the urine contained no others saccharid than levulose in appreciable 
quantity. 

Kiilz, in 1886, wrote to the patient asking for five liters of her urine, and 
found that the urine fermented slowly but completely on addition of yeast, form¬ 
ing alcohol and carbonic acid ; that it had a sweet taste on concentration ; and 
that with phenylhydrazin chlorate and sodium acetate it yielded an osazone 
that melted at 205° C. (401° F.), and had the formula C 6 H 12 0 6 . It yielded 
also Selivanoff’s reaction and turned the ray of polarized light to the left. 
This would have assured an ordinary person of the identity of the saccharid 
with levulose. Kiilz found also that levulose in “ absolutely pure, hard crys¬ 
tals ” dissolved in water was again precipitated by lead acetate, and that the sac¬ 
charid in the urine of Mrs. F. was precipitated by this salt only on addition of 
ammonia—a difference that, as he himself, with all his doubts, remarked, 
might well depend on the different solvent mediums. 

Le Nobel mentions a case of ?nallosuria in a diabetic patient of sixty-one 
years, whose digestion of fat was much impaired. Von Ackeren found maltosuria 
in a case of carcinoma of the pancreas, and Wedenski possibly also saw such 
a case. Further investigations seem necessary, especially in view of the fact 
that extirpation of the pancreas causes in dogs only glycosuria. 

Laios, found by Leo in association with glucose in three severe cases of dia¬ 
betes, reduced (less than glucose), turned the ray of polarized light to the left, 
yielded an osazone with Fischer’s test, but did not ferment and had no sweet 
taste. 

If there has been much to say with regard to the fate of carbo¬ 
hydrates in normal and diabetic organisms, we may state in com¬ 
paratively few words what is necessary with regard to the fats, 
however important an item they constitute in the dietary of a dia¬ 
betic patient. We know of no direct changes in the metabolism of 
fat in cases of diabetes. 


210 


DIABETES MELLITUS AND GLYCOSURIA. 


We have seen that fat does not increase the glycogen in the liver 
or elsewhere. We also know that it does not increase the glyco¬ 
suria in any cases of diabetes. 

The absorption of fat, as has already been mentioned, is, in most 
cases of diabetes, normal. Fat is decomposed, as usual, by the bile 
and the pancreatic juice into triglycerid, free fatty acids, and soaps. 
In the chyle it is again found almost exclusively as neutral fat, and 
is stored in the liver and in the muscles. We have seen that its fate 
afterward is unknown, and that there are various opinions, differing 
from the one expressed by Nasse, who believes that it is utilized 
and oxidized exclusively in the liver, to which the fat would have to 
return when once stored anywhere else. 

Two qualities of fat—its high caloric value and that of not in¬ 
creasing the hyperglycemia—make it an excellent food for diabetics. 
Unfortunately, it is impossible to utilize practically to the full ex¬ 
tent what might theoretically be expected from this kind of food. 
Fat can be tolerated only in quantities that are far below the caloric 
needs of the organism. Then fat does not protect the proteids of 
the organism as powerfully as carbohydrates do. 

The circumstance that the same number of calories given in the 
form of carbohydrates diminish the consumption of proteids much 
more than an equal number of calories in the form of fat has been 
demonstrated by Voit, who was able to reduce the excreted nitrogen 
with 15 per cent, by the administration of carbohydrates, but only 
with 9 per cent, by the administration of fat. 

I insert the following table, compiled from Kaiser’s researches : 


Time. 

Daily Food in 

Grams. 

Calories. 

Nitrogen in 
Urine 
and Feces. 

Gain 

or 

Loss. 

Nitrogen. 

Fat. 

Carbo¬ 

hydrate. 

I. Four days, . . 

21. l8 

71-65 

338.2 

2593 

20.15 

+ 1-03 

II. Three days, 

21-53 

217.9 

O. 

2577 

24-5 1 

—3-05 

III. Three days, 

21.10 

70.37 

338-2 

2581 

20.17 

+O.93 


The most curious fact, that the nitrogen in the urine is sometimes increased 
by the ingestion of fat, has several times been observed, in contradistinction to 
the power of conserving proteid, which certainly belongs to some extent to tat. 
Voit believes that this happens only with a small supply of proteids and a large 


















METABOLISM AND NUTRITIVE NEEDS. 


21 I 


supply of fat, but Weintraud’s tables do not seem to corroborate this view. 
Voit attributes to the fat two qualities with opposite results : It has the well- 
known effect of conserving proteids; but, on the other hand, it has a tendency 
to increase the circulating proteids. Weintraud refers to an analogous 
phenomenon in one of Nasse’s experiments : A dog receives a certain quan¬ 
tity of phenol, excretes part of it unchanged and oxidizes the remainder to 
hydrochinon ; with a larger supply of fat the unchanged phenol decreases and 
the hydrochinon increases. Nasse considers that the oxidation of fat pro¬ 
duces free atoms of oxygen. Still, we do not know how this is done, and we 
stand before a most curious enigma. I should find it interesting to know how 
the diaceturia and the glycosuria resulting from proteids in a severe case of 
diabetes are influenced by a larger supply of fat, when fat increases the nitro¬ 
gen of the urine. 

An ordinary civilized person can not eat more than a certain 
limited quantity of fat,* and—worse luck for the diabetic patients !— 
it is not meat, but bread and potatoes (i. e., carbohydrates), that 
help him to eat more. A comparatively limited allowance of bread 
—viz., from 80 to ioo grams a day—markedly increases the capa¬ 
bility of eating a good deal of fat; but even then patients generally 
can not take more than 200 or 250 grams of this in the twenty-four 
hours f without nausea and digestive disturbances. 

The formation of fat within the organism in cases of diabetes is 
impaired by the passing off in the urine of a part of the carbohy¬ 
drates of the food which otherwise might form fat. In the severe 
stage a deficit arises in a like manner in the formation of fat from 
proteids, which may occur in different ways, but which certainly 
takes place in consequence of the intermediate formation of glyco¬ 
gen. It is, by the way, possible that a better knowledge of the 
details of the formation of fat from carbohydrates and from pro- 


* The Arctic nationalities are capable of devouring large quantities of fat. In 1868 
I traveled through Lapland with no other company than a Lap for a servant. I was on 
one occasion about to throw away quite a quantity of butter which began to be rancid. 
The Lap protested against this waste, and, on permission, devoured the whole amount at 
once without the addition of bread or of anything else. 

•f The ordinary articles of food containing the largest percentage of fat are as follows : 
Butter, with about 84.4 per cent, of fat and from 0.1 to 0.5 per cent, of carbohydrate. 


Olive-oil, “ 

99 

4 4 

4 4 

o.x 

4 4 

4 4 

Lard, “ 

76 “ 

4 4 

4 4 

0. 

4 4 

44 

Rich cheese, “ 

30.5 

44 

44 

i -5 

44 

4 4 


“ Lipanin ” is olive-oil with about six per cent, of free fatty acid, and is said to taste 
better and be easier of digestion than neutral olive oil. 



212 


DIABETES MELLITUS AND GLYCOSURIA. 


teids in the normal organism would contribute to a solution of some 
of the many mysteries of diabetes. A consideration of the forma¬ 
tion of fat within the diabetic organism leads me to discuss the close 
connection that, notwithstanding the restriction of this formation, 
undoubtedly exists between adiposity and diabetes, and also the 
connection of both of these dystrophies with the gouty dystrophy. 
It would be pleasant and convenient to be able to indicate the 
nature of this connection by saying that the deficient power of 
oxidizing fat goes hand in hand with a deficient power of oxidizing 
carbohydrates, and that both these deficiencies are closely related 
to the deficient power of oxidizing proteids. But, with all the 
weakness of our present position, with our exceedingly imperfect 
knowledge of the pathogenesis of each of the three dystrophies, we 
now know enough to understand how premature it would be to 
indicate in such a manner the deep mystery of the relation referred 
to. The worst diabetic can oxidize fat and other substances in 
enormous quantities. The theories lately emanating from Germany 
in this connection belong, in all their ingenuity, in the domain of 
pure speculation. 

Since the end of the 18th century physicians now and then have 
observed that the blood exhibits a grayish color in cases of severe 
diabetes, and this color has been found to be due to the presence 
of an increased quantity of fat in minute particles. Diabetic lipemia 
has reached as high as 11.7 per cent, in man (Lecanu) and 12.3 per 
cent, in the dog (D. Gerhardt). It is known that the customary 
0.2 or 0.3 per cent, of fat in the blood may normally increase enor¬ 
mously after digestion. Still, there seems to be no doubt that some 
diabetes, like tuberculosis and alcoholism, sometimes causes the ap¬ 
pearance of a still larger quantity of fat in the blood, a true hyper¬ 
lipemia , and, sometimes, though only in rare cases, a consequent 
lipuria. This may be a phenomenon connected with the toxic, 
“protoplasmatic” disintegration of proteids; but at present our 
knowledge of the matter is restricted to what I have already 
mentioned. 

Alcohol must not be left out of consideration in a discussion of 
human food. It has high caloric value ; a gram yields seven calories 
gross. When large amounts are taken, about ninety per cent, of 


METABOLISM AND NUTRITIVE NEEDS. 


213 


these calories are utilized (Strassman) ; when the amounts are small, 
probably more is utilized (Hirschfeld). These calories are, how¬ 
ever, not of high quality ; Miura has shown that alcohol protects 
the proteids much less than the same caloric amount of carbohy¬ 
drates, and less even, it seems, than the same caloric amount of fat. 
In large amounts it acts as a protoplasmic poison, with a well-known 
deleterious influence in various respects, and in such amounts 
lessens the power of assimilation both in cases of diabetes and under 
other conditions. In most cases of a gram of pure alcohol per 
kilogram of bodily weight is a fair allowance a day; double this 
amount is never to be exceeded for habitual use. Even in these 
amounts alcohol ought always to be taken much diluted, to avoid 
irritation of the mucous membranes and of other structures. In this 
condition and in the doses stated it will do no harm and some good, 
especially to diabetics. It economizes fat, and if any one, after taking 
from twenty to thirty grams of alcohol a day, suddenly observes 
absolute abstinence, he will always, ceteris paribus , lose in bodily 
weight. In such amounts alcohol does not lessen, but rather in¬ 
creases, the power of assimilating carbohydrates (Kulz). If recent 
investigations (of Hirschfeld) have not corroborated the claims for 
alcohol that it facilitates the absorption of fat, there can be no doubt 
about its value in small amounts in facilitating the ingestion of larger 
quantities of fat and in increasing the appetite in general. The 
many and terrible sins that mankind has committed with alcohol 
ought not to make us blind to its real and most important advan¬ 
tages. There are at present in this country (Sweden), as there have 
always been, a great many drunkards, who ruin themselves with 
alcohol, and a great many cranks with an unwise and blind passion 
for total abstinence. 

As a faulty metabolism of carbohydrates distinguishes the mild 
stage of diabetes from a normal condition, so a faulty metabolism of 
proteids distinguishes the severe stage from both the mild stage and 
the normal condition. Unfortunately, a host of questions, that can 
not at present be answered, present themselves with regard to the 
fate of proteids both in the normal and in the diabetic organism. 
We do not know much more than that proteids may form proteids, 


214 


DIABETES MELLITUS AND GLYCOSURIA. 


fat, and carbohydrates.* The differences with regard to processes 
both of disintegration and of synthesis between different kinds of 
proteids, especially between the simpler proteids and those of a 
more complicated molecular constitution, the proteids sensu stnc- 
tiori (nucleins, mucins), the metabolic differences between the 
various tissues, the successive molecular steps on the way to com¬ 
plete oxidation, etc., are, for the greater part, unknown. 

Our next most important task will be to become better acquainted 
with the conditions of production and consumption of the three 
substances, acetone, diacetic acid, and ^-oxybutyric acid, in cases of 
diabetes. We have good general and special reasons for consider¬ 
ing them to be momentarily present even in healthy organisms, 
though the /J-oxybutyric acid, the mother-substance of the others, 
is normally quickly converted into diacetic acid, this acid into 
acetone, and acetone into carbonic acid and water. I shall return 
to this subject later. 

The difference in the metabolism of the proteids between the mild 
and the severe stage of diabetes begins in the liver. I have stated 
that if in the mild stage the carbohydrates are restricted below the 
patient’s limit of assimilation, the formation of glycogen in the 
liver in great probability takes place just as it does in a normal indi¬ 
vidual upon the same diet. In cases of severe diabetes, however, 
the formation of glycogen is restricted under all dietetic conditions, 
and even a part of the products of proteids passes off in the urine 
as glucose. 

The details of the formation of carbohydrates from proteids are 
not known. We do not know if all the glucose derived from pro¬ 
teids must first become glycogen, but we have good reason for 
believing that there is no such necessity and that proteids can 


* The formation of proteids from peptones and albuminoids need not detain us, and we 
have already spoken of the formation of carbohydrates from proteids. There is still some 
slight doubt whether proteids can or can not form fat directly and without first forming 
glycogen, notwithstanding the cellular manifestations in regressive metamorphosis or after 
certain poisons, the formation of the acid of palmitin (Salkowski) and other productions 
after death (Salkowski, Lehmann), the supposed formation of fat from proteids in larvae 
(Hofmann), the abundant formation of milk even with an exclusive diet of meat in 
bitches (Subbotin, Voit, Kemmerich), and the disappearance in the organism of carbon 
with a similar diet (Pettenkofer and Voit, E. Voit). 



METABOLISM AND NUTRITIVE NEEDS. 


215 


directly form other carbohydrates than glycogen. Hammarsten 
isolated (from the pancreas, the liver, and the mammary gland) a 
nucleo-proteid which, when boiled with a diluted mineral, yielded 
a reducing substance that was proved to be a pentose. Hammar¬ 
sten admits the separation of a molecule of carbohydrate from the 
proteids of a more complicated structure (nucleins, mucins). Pavy 
considers the proteids glucosids that, boiled with diluted acids, 
yield saccharids and proteids of less complicated structure, and has 
produced carbohydrates from the albumen of eggs and from fibrin. 
Kravkow’s researches have led to similar conclusions with regard to 
some kinds of proteids. Kassel produced formic acid and levulinic 
acid by the action of sulphuric acid on nuclein. Levulinic acid has 
always shown itself as a derivative of carbohydrates. 

It is the presence of derivatives of proteids in the urine that dis¬ 
tinguishes severe from mild diabetes. The glucose in severe cases 
is partly derived from proteids ; the acetone, the diacetic acid, and 
the /5-oxybutyric acid in such cases are believed to be derived 
exclusively from proteids. 

If in a case in the mild stage the carbohydrates of the food are 
restricted below the patient’s limit of assimilation his urine, as is 
well known, remains free from glucose and does not , so far as we 
know at present , differ from the urine of a normal person living on 
the same diet. 

For practical reasons I here deviate from the straight line of ex¬ 
position to show the truth of this last assertion. 

Among certain derivatives of proteids in the urine in the mild 
stage we are chiefly interested in urea, uric acid, and acetone (the 
diacetic and /5-oxybutyric acids belong exclusively to the severe 
stage). 

Acetone was first discovered in a case of severe diabetes. It is 
undoubtedly increased in such cases. Engel found 2.8 grams, 
which is a rare figure. In normal individuals the daily excretion is 
only about 0.01 gram (v. Jaksch); but it is often increased in 
children, whose breath, by the way, sometimes under apparently 
normal conditions smells of acetone. It is increased also with 
lactosuria during lactation, being probably derived from casein 
(Guckelberg, v. Jaksch), and after the ingestion of certain poisons, 
during starvation, in febrile states, in eclampsia and epilepsy, lyssa, 


2 16 


DIABETES MELLITUS AND GLYCOSURIA. 


cachexia, disturbances of digestion, and mental diseases. It is 
normally increased when carbohydrates are excluded from the diet 
and with a purely animal diet. Von Jaksch states that in some mild 
cases of diabetes it does not occur in larger quantities than in nor¬ 
mal individuals using the same food, and Hirschberg’s researches 
point to a similar result. At present it is not proved that there is 
any increase of acetone at all in the mild stage of diabetes, and, 
even in that event, it is not known under what circumstances or in 
what class of cases (see below). 

As to urea, it is now known that in the large majority of cases 
of diabetes it is not present in the urine in larger quantities than in 
normal individuals under the same dietetic conditions. Only in the 
very severe cases with the toxic or protoplasmic disintegration of 
tissues is the patient supposed to excrete more urea than a normal 
person upon the same food. 

The quantity of uric acid, about which only the newest analytic 
methods give reliable information, varies greatly in normal indi¬ 
viduals. Naunyn and Riess, by a method of their own, found from 
o. 16 to 1.05 grams ; Kiilz, by the same method, from 0.06 to 0.76 
gram ; Bouchardat, more than three grams ; Hartz, in six cases of 
diabetes, found at the utmost between 1.5 and 2 grams of uric acid 
in the urine in twenty-four hours. Neither from these, nor from 
Bischofswerder’s, nor any other researches can it be concluded that 
a greater or lesser excretion of uric acid takes place in diabetics than 
in normal individuals. To gain some notion of the difference between 
normal individuals and diabetics in this respect, it would be necessary 
to compare a large number from each of the two classes under the 
same dietetic conditions, and especially with the same quantity of in¬ 
gested nucleins. On account of the absence or presence of sediment, 
and on no better basis than “ uroscopy,” it has been said that uric 
acid is diminished in the severe stage and increased in the mild stage 
of diabetes. Some writers have also (since 1855) spoken of a “ dia¬ 
betes alternans ,” with alternation in the excretion of large quantities 
of uric acid and of glucose (Claude Bernard, Bouchardat, Brogniart, 
Budde, Coignard, Charcot, Ebstein). I am far from certain that 
such an alternation takes place, and I am pretty certain that its 
existence has never been proved. As is well known, the sediment 
is by no means an adequate expression of the quantity of uric acid 


METABOLISM AND NUTRITIVE NEEDS. 


217 


present. A urine containing a greater amount of uric acid may 
keep the whole amount in solution, while another urine containing 
less uric acid may present a part of it in the form of a sediment. 
In mild gouty cases of diabetes the urine often contains consider¬ 
able sediment. All that can at present be safely asserted is that a 
marked sediment of uric acid indicates a mild case of diabetes, and 
that such a sediment is absent from the pale greenish-yellow urine 
of severe cases. 

Kreatin was found by Winogradoff in small quantities and by Sena¬ 
tor in large quantities in diabetic urine (up to two grams a day). 
From their researches, and from those of Bunge and St. Johnson, 
we infer that kreatin and kreatinin are in most cases of diabetes 
(and apart from toxic disintegration of tissue), under the same diet¬ 
etic conditions, to be found in the urine in the same quantity as in 
normal urine. 

In mild cases the amount of ammonia does not exceed that which 
may be found normally with an abundant supply of proteids. Only 
in severe cases with “acidosis” does it attain large proportions, 
and it may equal as much as twelve grams in twenty-four hours— 
solely because the acids have a greater affinity for it than they have 
for urea. 

Boedeker found in diabetic urine a substance that he called 
alkapton, but which is found also in the urine of normal children 
and of other nondiabetic persons. In some instances the sub¬ 
stance found may possibly have been pyrocatechin. It is also 
represented by uroleucin and glycosuric acid, and is otherwise 
known as homogentisinic acid. It can not be said to bear any 
special relation to diabetes; according to Baumann and Walkow, it 
is formed in the bowel under the influence of certain micro¬ 
organisms. 

Hippuric acid has been found in diabetic urine (from o. 1 to 1 
gram) by Lehmann ; it is found also in normal urine, and is in¬ 
creased in febrile states, in diseases of the liver, and in neuroses. It 
arises in the course of the putrefaction of proteids, and may be found 
equally apart from as with diabetes, whenever putrefactive processes 
are taking place. 

The low fatty acids (formic, acetic, butyric, propionic) are but 
rarely found in diabetic urine recently passed (v. Jaksch); they are 

15 


2 18 diabetes mellitus and glycosuria. 

sometimes found in normal urine and, according to Rumpf, they are 
present in normal quantities in mild, but in increased quantities (up 
to ten grams) in severe cases. Purely diabetic lipaciduria is a 
feature exclusively of such cases. 

Lipuria is sometimes found in normal persons after the ingestion 
of large amounts of fat, and is found in association with the most 
widely different pathologic conditions, chiefly after the taking of 
certain poisons and in cachectic or marantic states. Purely dia¬ 
betic lipuria, like purely diabetic lipaciduria, is a feature of severe 
cases. 

Lactic acid in its two slightly different modifications may occur in 
the urine in cases of diabetes. Minkowski in a severe case found the 
levogyrate acid in the blood ; Rumpf in a similar case found it in 
the urine. We have already seen that lactaciduria is a common 
phenomenon in conjunction with glycosuria after some poisons; it 
has also been found in cases of acute yellow atrophy of the liver. 
Colasanti and Moscatelli found lactic acid in small quantities in the 
urine of soldiers after forced marches. We are at present too little 
acquainted with the conditions for the appearance of lactic acid in 
the urine to decide its relation to diabetes. Still, it seems certain 
that it may appear under other conditions. 

We undoubtedly find in cases of diabetes—especially, as it seems 
to me, in mild cases—an increased amount of oxalic acid in the 
urine. I have sometimes seen quite an enormous number of the 
small crystals of calcium oxalate in cases of simple glycosuria, when 
an abundant supply of carbohydrates has given rise to only a trace 
of glucose in the mixed urine. I am much more inclined to accept 
(with Prout) an alternation between oxaluria and glycosuria in cer¬ 
tain cases than an alternating excretion of glucose and uric acid. 
Furbringer saw oxaluria and oxaloptysis in a diabetic patient. 
There are many records of oxaluria in cases of diabetes, and it may 
exist without being discovered by the microscope, the calcium 
oxalate being kept in solution by the acid phosphates, which are 
often present in large quantities in the urine of diabetic patients eating 
much meat. Apart from alimentary and normal oxaluria and the 
“symptomatic” oxaluria associated with some other diseases and 
pathologic states, and apart from diabetic oxaluria, there is a form 
known as (Cantani’s) idiopathic oxaluria with its neurasthenic and 



METABOLISM AND NUTRITIVE NEEDS. 


219 


slight dystrophic symptoms. This idiopathic glycosuria is probably 
identical with the oxaluria found in neurasthenic individuals with or 
without glycosuria. On the other hand, and so far as is known at 
present, there are many cases of glycosuria or diabetes without 
oxaluria. 

The abundant ingestion of proteids in cases of diabetes, often 
associated with habitual constipation and protracted retention of the 
feces in the bowels, causes an increase in the products of putrefac¬ 
tion. We thus find sulphuric acid combined with aromatic alco¬ 
hols (phenol, indoxyl, etc.) and the combined glycuronic acids in¬ 
creased. The sulphuric acid in the sulphates is also increased by 
the customary abundant amount of animal food ; but we have no 
reason to believe that in mild cases of diabetes, and apart from toxic 
disintegration, the whole amount is more greatly increased than it 
would be under similar circumstances in nondiabetic individuals. 
The total acidity, too, is often increased in cases of diabetes, as 
Derignac and others have noted, bub in mild cases only from the 
causes just mentioned. In severe cases the diacetic and /3-oxybu- 
tyric and other acids contribute to the increase of the total acidity. 

Phosphaturia will be considered later. 

Inosite is found in cases of diabetes, but also in all states 
attended with polyuria. Reichardt’s dextrin was found in the urine 
in a case of mild diabetes, but it is not known whether or not it has 
any connection with diabetes. The same is true with regard to 
Leube’s glycogen, which may perhaps be identical with Reichardt’s 
dextrin. Lemaire’s isomaltose is not well known, and Wedenski 
found in normal urine something that may be maltose. Gum or 
achrooglycogen is also found in normal urine (Landwehr, Weden¬ 
ski, Amann). 

Kiilz and T. Vogel found pentoses (from 0.25 to 0.43 gram a 
day) in cases of severe diabetes. The test for phenylhydrazin in 
normal urine also yields some crystals of osazone, which melt at 
165° C. (329° F.), and which probably are pentoses (E. Holmgren). 

Leon Kalm found urobilin absent in two severe cases of diabetes. 
Vogel and Neubauer mention this absence in normal urine. 

M. Ch. Ulrich has come to the conclusion that leucin and tyrosin 
are present in normal urine, but absent in cases of severe diabetes. 
(The crystals seen by Roque, Devie, and Hugonenq in the liver, 


220 


DIABETES MELLITUS AND GLYCOSURIA. 


then, could not have been leucin and tyrosin.) Whether the two 
substances are present in or absent from the urine in mild cases of 
diabetes is not known. 

In severe cases of diabetes the diastatic and the peptic ferment 
have been found to be increased in the urine (Hoffmann, Stadel- 
mann, Leo, and others). Lepine found no increase of the diastatic 
ferment, and nothing is known of such an increase in mild cases. 

Albic found diabetic urine strongly toxic (from ptomains, di- 
amins, etc.). Neubauer and Vogel mention that diabetic urine apart 
from cachexia is not more toxic than other urine, which indicates 
that the increase of toxic substances is a feature of severe cases ex¬ 
clusively. 

From the foregoing brief exposition it may be concluded that we 
do not at present know of any pathologic substance that is invariably 
present in the urine in mild cases of diabetes.* 

Traube’s definition of severe diabetes is the best even to-day : A 
state that is attended with excretion of glucose in the urine, even when 
carbohydrates are excluded from the food, and when a pure diet of 
proteids (and of fat) is observed. It will be understood that this 
does not mean that severe diabetes is, while light diabetes is not, 
attended with the production of carbohydrates from proteids ; it 
having been proved long ago that proteids give rise to glycogen 
and thus indirectly (and perhaps also directly) to glucose, in all 
organisms, diabetic in any stage, or nondiabetic. In the mild 
stage, however, the patient, while losing (some of) the glucose 
derived from carbohydrates, has the power of assimilating at least 
all of the glucose derived from proteids. In the severe stage, 
though the patient always retains the capability of utilizing a part 
of the glucose derived from carbohydrates, he has lost the power 
of utilizing all of the glucose derived from proteids. 

On this point, again, we find that mild and severe diabetes are 
only stages of the same dystrophy, and that there are intermediate 
states representing the gradual transition from the one to the other. 
There are patients who, when carbohydrates are excluded from the 
food, present no glycosuria with a certain daily supply of proteids, 


* The substances whose connection with mild diabetes it seems most interesting to 
investigate are acetone, oxalic, glycuronic, and lactic acids. 




METABOLISM AND NUTRITIVE NEEDS. 


221 


but who again excrete glucose if the amount of proteids is in¬ 
creased, though carbohydrates are still excluded (Naunyn, Licht- 
heim, Troye, Weintraud). 

I wish, however, to insist most forcibly that the hyperglycemia 
and the glycosuria resulting from proteids do not constitute the 
most important metabolic difference between the mild and the 
severe stage of diabetes. The main and all-important difference 
between mild and severe diabetes is the production in the latter 
of certain acid toxins in the blood and in the urine. 

This brings us again to a consideration of that most interesting 
trio already touched upon : acetone, diacetic acid, and /?-oxybutyric 
acid.* The latter two substances, and especially the last, are im¬ 
portant factors in the acid diathesis, the “ acidosis,” existing in 
cases of severe, but not of mild, diabetes. 

All three substances, free from nitrogen as they are, originate in 
proteids, and seem to appear as soon as the organism, from some 
cause or other, attacks its own proteid tissues ; they all three appear 
during starvation, and in the course of different states producing 
inanition. 

Though there is little doubt as to the intimate connection of the 
three substances as representing different stations on the way to 
complete oxidation of molecules derived from proteids, the reason 
why the course of oxidation is interrupted in cases of severe diabetes 
and in some other states will probably continue for a long while to 
be a puzzle to every student of diabetes. There are good reasons 
for believing that the same disintegrated proteids as alone give rise 
to glucose in the urine in cases of severe diabetes also give rise 
to /3-oxybutyric acid and its derivatives, diacetic acid and acetone. 
The curves representing the glucose derived from proteids and 
the /3-oxybutyric acid show unmistakable parallelism (Naunyn). 
Any one that follows a case of diabetes in its development through 
the mild into the severe stage will gain the positive impression of a 


* Acetone [C 3 H 6 0 ] is a watery, strong-smelling, neutral liquid, boiling at 56.5° C- 
( 133 - 7 ° F.). 

Diacetic acid [C 4 H 6 0 3 ] is a thick, colorless, hygroscopic liquid, which is decomposed 
into carbonic acid and water at a temperature below ioo° C. (212° F.). 

/3-oxybutyric acid is a colorless liquid of the consistency of syrup, which by oxidation 
easily yields acetone. Boiled with acid water, it yields a-crotonic acid and water. 



222 


DIABETES MELLITUS AND GLYCOSURIA. 


parallelism between the glycosuria due to proteids on the one hand, 
and the three substances named on the other. The patient in the 
distinctly mild stage can usually take some carbohydrate without 
the development of glycosuria. During this state there is no 
/3-oxybutyric acid and no diacetic acid in the urine so long as the 
patient utilizes a sufficient amount of calories in his food, and there 
is under these conditions no more acetone than in the urine of a 
normal person using the same kind of food (see below). As the 
dystrophy advances, the amount of acetone in the urine probably 
increases before either of the acids has made its appearance. 
There is at present some uncertainty as to the exact place in the 
development of the glycosuric dystrophy where this happens (see 
below). So long as the patient, with exclusion of carbohydrates 
from the food, becomes free from glycosuria, he presents no diacet- 
uria with a sufficient supply of calories. After some time, how¬ 
ever, in slowly developing cases,—generally some years after the 
beginning of the diabetes,—the patient, even during a period of ex¬ 
clusion from the food of carbohydrates, exhibits a distinct, though 
slight, glycosuria. At this stage the physician finds for the first time 
Gerhardt’s reaction in the urine with ferric chlorid, though he has 
taken care to provide his patient with an adequate supply of calo¬ 
ries. There is now also an increased amount of acetone in the urine, 
and there is a faint odor of this substance on the patient’s breath. 
The urine contains no /J-oxybutyric acid. The patient is likely to 
lose flesh, but he is only in the first part of the severe stage, and 
he is often able to maintain his weight. There is a possibility that 
this can be effected only by some increase in the amount of fat 
covering a loss of proteid. As the dystrophy advances the glyco¬ 
suria due to proteids increases, and pari passu Gerhardt’s reaction 
deepens in intensity until it gives rise to a dark bluish-red color, 
the breath smells more and more strongly of acetone, and autoph- 
agy becomes more and more manifest. Long before these last 
symptoms become extreme, but, in slowly developing cases, often a 
considerable time after the transition from the mild to the severe 
stage, the physician, after having removed the glucose from the 
urine by fermentation, and after having removed other levogyrate 
substances than /S-oxybutyric acid (combined glycuronic acids) by 
precipitation with ammonia and lead acetate, still finds a distinct 


METABOLISM AND NUTRITIVE NEEDS. 22 3 

levogyration in the polarimeter. He can afterward observe how 
the /5-oxybutyric acid increases in quantity as the case advances 
in the severe stage. 

It has generally been accepted that when /5-oxybutyric acid, the 
mother-substance of diacetic acid and acetone,* appears in the urine, 
these latter substances are certain also to be present. It has also 
been quite generally accepted that /5-oxybutyric acid is present 
only in urine that yields a marked Gerhardt’s reaction, or, in other 
words, in urine that contains a considerable amount of diacetic acid. 
In general, the rule holds good that when one finds the /5-oxybu¬ 
tyric acid,—which undoubtedly denotes a more advanced period in 
the severe stage and a greater autophagy than either of the two other 
substances,—these are also to be found. It also seems certain that 
when diacetic acid is found, which is not rarely the case when no 
/5-oxybutyric acid is present, acetone is usually found in an abnor¬ 
mally increased quantity. The appearance of the latter substance 
is a less grave phenomenon than that of diacetic acid, and this, again, 
is less grave than that of /5-oxybutyric acid. It seems certain, 
however, that the quantitative relations of the three substances are 
not fixed, and that one can not, from the quantity of one, reach a 
conclusion as to the quantity of either of the others. It is 
especially worth remembering that the common idea with regard to 
a necessarily pronounced Gerhardt’s reaction in all urine containing 
/5-oxybutyric acid is a false one. I have several times found an 
unmistakable amount of /5-oxybutyric acid in urine that has not 
yielded with the solution of ferric chlorid the dark bluish-red 
color of considerable quantities of diacetic acid, but only a light, 
transparent red. Naunyn and Albertoni have made analogous 
observations. I find in Neubauer and Vogel’s last edition a note 
(after Stadelmann ?) that /5-oxybutyric acid may be present without 
any diacetic acid at all. This certainly is not a common occurrence. 

Gerhardt’s reaction, if pronounced, indicates constant danger 
of coma. If the reaction is absent or only faint, this seems to 
indicate the absence of any considerable quantity of /5-oxybutyric 


* Minkowski demonstrated the relation of /3-oxybutyric acid as the mother-substance of 
diacetic acid and acetone. By administering /5-oxybutyric acid to diabetic dogs he caused 
the appearance or the increase of both of the other substances in the urine. 



224 DIABETES MELLITUS AND GLYCOSURIA. 

acid, and, unless the general state is extremely bad, there is then 
no immediate danger of coma. What the actual conditions are in 
those extremely rare cases in which a strong acidosis has been 
found as a result of the presence of some other acid than / 3 -oxy- 
butyric (and diacetic) acid, I do not know. 

The /3-oxybutyric acid in the urine of the three substances under . 
consideration alone reaches large amounts. One hundred grams in 
twenty-four hours is not very rare ; seventy grams is not uncom¬ 
mon. Kiilz found 226 grams in one case. The relation between 
the quantity of /3-oxybutyric acid in the blood and the quantity in 
the urine is not clearly known. Hugonenq found 0.427 per cent, 
in the blood and 0.448 per cent, in the urine. In the enormous 
majority of cases the acid diathesis—the “ acidosis,” as Naunyn calls 
it—are determined chiefly by the amount of / 3 -oxybutyric acid. 
This danger is also, and to a great extent, determined by the 
general state. The same amount of acid which one patient is able 
to endure for months may kill another in a few hours. As soon as 
the urine for twenty-four hours contains as much as twenty grams 
of /3-oxybutyric acid there may be danger of coma.* 

Diacetic acid is found throughout the whole of the severe stage 
and, as a mere diabetic phenomenon, not in the mild stage at all. If 
a healthy person be given an exclusive diet of proteids or of proteids 
and fat, no diaceturia arises so long as a sufficiently large number 
of calories for the nutritive balance is ingested ; but the inges¬ 
tion of a sufficient supply of calories without carbohydrate in the 
food is a difficult task. A deficit readily arises, of which from 83 
to 93 per cent, is covered by the consumption of the patient’s own 
fat, while the remainder is furnished by that of his own proteids 
(Lusk, Miura, v. Noorden). With this kind of disintegration of the 
latter diaceturia begins and Gerhardt’s reaction with the urine will 
appear. In this manner diaceturia will arise in cases of mild dia¬ 
betes, just as it does in cases of ulcer of the stomach or of appen¬ 
dicitis or of seasickness in the progress of more or less pronounced 
starvation. Unless the starvation is very severe, however, the solu- 


* This danger can also be estimated by the amount of ammonia excreted. As soon 
as the quantity reaches 1.5 grams in twenty-four hours the acidosis is sufficient, in con¬ 
junction with a greatly enfeebled general state, to produce coma. 



METABOLISM AND NUTRITIVE NEEDS. 22 5 

tion of ferric chlorid will not cause the typical purple or bluish-red 
color to appear in the urine. When the ferric chlorid falls drop by 
drop into the urine, it becomes surrounded by a red zone ; when the 
phosphates of iron afterward sink, the liquid above has a brownish- 
red, sherry color. 

Even in the worst cases the diacetic acid in the urine hardly ever 
reaches twenty grams in the twenty-four hours, and, though it must 
be considered as contributing to the acidosis and to the coma, it is 
far less efficient in this respect than the /?-oxybutyric acid. 

It is an important circumstance that, so far as I have been able 
to ascertain, the whole severe stage of diabetes, per se and apart 
from other causes, is attended with diaceturia. Whenever I see 
a frank Gerhardt’s reaction with the urine of a patient receiving 
an abundant supply of calories with his food,—which generally 
presupposes a certain amount of carbohydrate,—I know at once 
that an exclusive diet on meat and fat will not remove the glucose 
from his urine. On the other hand, the absence of diacetic acid 
from the urine almost invariably indicates that the case is still in 
the mild stage, and that a number of days * of abstinence from car¬ 
bohydrates will cause the sugar to disappear from the urine. There 
are, however, exceptions to this rule. Also with regard to diacet¬ 
uria, it is known that there are individuals living on the border¬ 
land between the mild and the severe stage of diabetes. I have seen 
patients who, with an abundant supply of mixed food, presented a 
large quantity of the glucose in the urine, but no diacetic acid, and 
who, with an exclusive but quite adequate supply of meat and fat, 
continued to excrete a small amount of glucose, and then also ex¬ 
hibited slight diaceturia. I take it that these individuals are able 
with an abundant supply of carbohydrates to protect their own pro- 
teids from the disintegration that at once gives rise to both glyco¬ 
suria and diaceturia ; all the glucose excreted with such a diet being 
derived from carbohydrates. When carbohydrates are strongly 
diminished or excluded, the glycosuria due to them ceases, but the 
patient is no longer able to protect his own proteids, the fat being 

* The length of the period of abstinence from carbohydrates for the necessary removal 
of the glucose from the urine varies according to the patient’s power of assimilation, and 
probably, also, according to the storage of glycogen and to other causes of an unknown 
nature. 



226 


DIABETES MELLITUS AND GLYCOSURIA. 


less efficient for this purpose than carbohydrates. He excretes only 
a small quantity of glucose, but this is now derived from the dis¬ 
integration of his own proteids, and the diacetic acid has the same 
origin. 

The difficulty of demonstrating the presence of acetone in the 
urine, and the still greater difficulty of determining the quantity 
produced in twenty-four hours,* have given rise to much uncer¬ 
tainty with regard to many important points connected with this 
substance. It is not known in what cases of diabetes acetone, as a 
mere diabetic phenomenon, is abnormally increased. Unlike diacetic 
and /3-oxybutyric acids, acetone is also found, though only in small 
quantities, in normal urine. It is certain that in a great many cases 
of fully developed but mild diabetes there is no increase of acetone 
with an abundant supply of carbohydrate. Von Jaksch found only 
the normal, small quantity of acetone in cases with an excretion of 
from 250 to 300 grams of glucose. On the other hand, it seems 
probable that an increased amount of acetone may appear in the 
urine in mild cases. One may sometimes perceive a faint but distinct 
odor of acetone on the breath of patients in the mild stage, even 
when they seem to be receiving a supply of calories sufficient for the 
maintenance of the nutritive equilibrium. When any person, dia¬ 
betic or not, excludes carbohydrates from his food and lives on meat 
and fat, the amount of acetone in the urine always increases (Hirsch- 
berg and others). This occurs more readily in diabetics than in 
healthy individuals (Rosenfeld), but even in healthy individuals it 
may cause an excretion of 0.7 gram in the twenty-four hours. The 
addition to the food of sixty grams of glucose or of starch causes 
the acetonuria to disappear.f The excretion of acetone in the urine 
is certainly of smaller significance than the excretion of diacetic or 
of / 3 -oxybutyric acid. If, with a sufficient supply of calories from a 
mixed diet, including a fair amount of carbohydrates, acetonuria 
exists at all in the mild stage, this certainly must occur in cases not 
far from the boundary between this and the severe stage. 

It is a most important fact that the whole trio of acetone, diacetic 


* Acetone being constantly exhaled through the lungs, the determination of the 
quantity excreted necessitates an analysis of the expired air. 

| Mannite in considerable amounts also causes acetonuria to disappear (Hirschberg). 




METABOLISM AND NUTRITIVE NEEDS. 2 2/ 

acid, and / 3 -oxybutyric acid seem to be more easily produced with 
an exclusive diet of fat and proteids than when carbohydrate is 
added. Dr. D. Gerhardt (see Naunyn) has observed that the same 
insufficient supply of calories in the diet causes the appearance of 
more / 3 -oxybutyric acid in the urine if made up of proteids and fat 
alone than if derived from a mixed diet, consisting in part of carbo¬ 
hydrates. Hirschberg has proved the analogous fact with regard to 
acetone, and the same is probably true also of diacetic acid. It is 
a common phenomenon that Gerhardt’s reaction perceptibly in¬ 
creases in diabetic urine when the patient is deprived of carbohy¬ 
drates and is put on a strict animal diet. 

Free fatty acids (formic, acetic, butyric, propionic, valerianic), 
which in normal urine scarcely reach o.oi gram in the twenty-four 
hours, may in cases of severe diabetes be present in tenfold quan¬ 
tity (Rumpf). These acids are derivatives of proteids, and the dia¬ 
betic aciduria , as has been already mentioned, is a feature of the 
severe stage. 

The whole amount of acids—acetic, / 3 -oxybutyric, fatty acids, 
lactic acid, oxalic acid, phosphoric acid, sulphuric acid (in the 
sulphates and combined)—may reach a large quantity, and in the 
course of twenty-four hours equal forty or fifty grams of concen¬ 
trated sulphuric acid. 

The acid diathesis, the acidosis, causes an increase of ammonia 
in the blood and the urine in cases of severe diabetes, and the 
quantity in the urine, which normally is about 0.7 gram for twenty- 
four hours, may reach the enormous amount of twelve grams in 
cases of diabetes (Stadelmann). This shows the great variation in 
the individual ability to bear up under the acidosis and to resist its 
comatose influence ; even 1.5 grams of ammonia constitute a warn¬ 
ing of coma, and two grams are often quite a distinct forerunner of 
it. 

When in a severe case of diabetes the carbohydrates are 
restricted or are excluded, autophagy and loss of bodily weight 
increase ; glycosuria and generally polyuria diminish ; the urine, 
even when diluted to its previous volume, yields a more pronounced 
Gerhardt’s reaction, from the presence of an increased amount of 
diacetic acid ; and the polarimeter shows some increase in the excre¬ 
tion of / 3 -oxybutyric acid. Sometimes, in cases that had previously 


228 


DIABETES MELLITUS AND GLYCOSURIA. 


been free from albuminuria, one also finds that with the strict diet 
the urine begins to contain a small amount of albumin, probably 
from the effect of the acid toxins on the kidneys. 

There are in the literature, and especially from those who defend exclusion of 
carbohydrates, even in the severe stage, reports of a decrease of diaceturia with 
such a dietetic change. Thus, Troye * relates the case of a patient who, with 
mixed diet, excreted 658 grams of glucose and a moderate amount of diacetic 
acid in more than nine liters of urine in the twenty-four hours, but who, after five 
days of a strict diet, excreted a normal amount of urine, free from diacetic acid, 
but containing twenty-seven grams of glucose. Such a statement is so contra¬ 
dictory to all of my experience that I can only conclude that there must be 
some mistake. 

Stokvis seems to consider the occasional appearance of albumin in the urine 
after the exclusion of the carbohydrates from the diet as resulting from the 
decrease in the quantity of urine, so that a trace, previously undiscoverable, 
becomes appreciable with Heller’s nitric-acid test. Even after diluting the 
urine to its previous volume one finds sometimes, with a marked restriction of 
carbohydrates, a trace of albumin that did not appear previously. 

Azoturia f in cases of diabetes has been much spoken of. An in¬ 
creased amount of nitrogen may appear constantly in the urine in 
cases of diabetes from two entirely different causes. There may be 
an alimentary azoturia and a protoplasmic or toxic azoturia. 

Alimentary azoturia of diabetes is easy to understand, and is the 
only increased excretion of nitrogen in the mild stage. The dia¬ 
betic patient either ingests much less carbohydrate with his food or 
he again loses part of it in his urine, and he must make up for 
this by the ingestion of a larger amount of fat and proteids. The 
larger supply of proteids to a diabetic as to a healthy person neces¬ 
sarily leads to a larger excretion of nitrogen. This excretion may 
be temporarily increased in consequence of marked polydipsia and 
polyuria, which per se may for the moment increase the nitrogen 
in the urine. During somewhat longer periods, however, with suf¬ 
ficient food, the amount of nitrogen excreted in a case of diabetes in 
the mild stage does not exceed the amount of nitrogen ingested. 

The second variety of diabetic azoturia, toxic or protoplasmic azo- 


*“ Archiv fur experim. Path, und Pharm.,” 1890. 

f Among one hundred cases Bouchard found forty-seven with an ordinarily large 
amount of nitrogen in the urine, forty with an increased amount, and thirteen with a 
diminished amount. Such figures are not worth much, if they do not cover a considerable 
length of time. 




METABOLISM AND NUTRITIVE NEEDS. 


229 


tuna , is a feature of the severe stage exclusively ; but it has not yet 
been quite decided whether it occurs in all or only in advanced 
cases of this stage. Toxic azoturia, however, was known to Ber¬ 
nard, and was subsequently studied by Voit and Pettenkofer, 
Kiilz, v. Mering and Minkowski, Chauveau and Kaufmann, Gley, 
Thiroloix, and others. It is believed to be caused by the toxins, 
and chiefly by the acid toxins, in the blood, and their disintegrating 
influence on protoplasm. The most marked effect of this kind un¬ 
doubtedly is caused by /5 > -oxybutyric acid. For my part, I am 
inclined to believe that some toxic disintegration of protoplasm 
takes place throughout the whole of the severe stage, and that there 
is a slight toxic azoturia even in cases in which the /5-oxybutyric acid 
has not yet shown itself, a purely diabetic diaceturia being already a 
sign of toxic or protoplasmic disintegration. It will be no easy 
matter, however, to demonstrate in such cases a constant excess of 
nitrogen-excretion over nitrogen-ingestion. This seems to me, 
however, to have been fully done in dogs after total extirpation 
of the pancreas, and I consider unsustained the doubt remaining 
in some minds as to the very existence of a diabetic toxic dis¬ 
integration of tissue and the consequent azoturia. 

During coma the products of metabolism in the urine generally 
decrease. Miinzer and Strasser, however, observed the nitrogen 
increase. 

The present views on diabetic azoturia have been gradually developed by 
the labors of Mosler, Boecker, Thierfelder, Uhle, Reich, Rosenstein, Haugh- 
ton, and Gathgens (1853-1866), and within more recent years by the researches 
of Kiilz, Kratschmer, Pettenkofer and Voit, Frerichs, Lusk, Fr. Voit, Minkow¬ 
ski, v. Mering, v. Noorden, Weintraud, Borchert and Finkelstein, Gley, Thiro¬ 
loix, and others. 

The enormous amounts of animal food consumed by some diabetic patients 
sometimes cause the appearance of large quantities of nitrogen in the urine. 
Leube found 150 grams, Furbringer 163 grams of urea, and I found eighty 
grams of nitrogen (equal to 171 grams of urea ; from 13 to 16 per cent, of the 
nitrogen, however, belongs to other substances) in twenty-four hours. Such 
figures are rare, but large quantities of nitrogen in the urine are common in 
cases of diabetes. This fact favored the opinion that every diabetic patient 
excreted more nitrogen than he ingested, an opinion which for a long time 
prevailed, though the very analyses on which it was founded and the 
mathematic absurdities to which it leads, considering the average duration of 
life in mild cases of diabetes, ought to have led quickly to more rational views. 

It is evident that if a diabetic and a healthy individual ingest the same 


230 


DIABETES MELLITUS AND GLYCOSURIA. 


number of calories with their food, and the diabetic again loses a certain 
amount of them in the form of glucose in his urine, the food that is barely 
sufficient for the healthy individual will not be sufficient for the diabetic, and 
the latter will cover the deficit by expending a part of his own fat and a smaller 
part of his own proteids. He will then decrease in bodily weight, and his 
urine will contain more nitrogen than has been ingested and digested. The 
same would happen with the healthy individual if from his food were removed 
the number of calories represented by glucose in the diabetic’s urine. If, 
however, both individuals received the same amount of calories with a diet 
that permits the diabetic to utilizeThe whole amount, he will not, in the mild 
stage, excrete more nitrogen than the healthy individual. 

In the severe stage toxic disintegration of protoplasm is a priori not improb¬ 
able, and it seems almost impossible to explain the results of recent most 
laborious investigations without admitting its occurrence. 

It is not at all certain that even all of the common toxins in cases of diabetes 
are known at present, though those that are amply explain the comatose syn¬ 
drome. Then, just as there are instances in which levulose appears in the 
urine instead of the customary saccharid, glucose, there may be exceptional 
products of metabolism. In fact, the more one studies diabetes, the more will 
he be prepared for surprises. We must, therefore, not entirely close our minds 
against the possibility of correct observation in Rupstein’s (1874) and Kiilz’s 
{1875) cases of diabetes in which alcohol was excreted in the urine. It is 
impossible to presume, in either case, the occurrence of fermentation in the 
bladder, and there scarcely remains any other way of explaining the formation 
of alcohol than by accepting Rupstein’s theory of an oxidation of diacetic acid. 
Kiilz, who was about as skeptical as any right-minded person is justified in 
being, considered that the large amount of alcohol in the urine was proved in 
the case that he published. Still, he did not observe it himself; but Dr. 
Guckelberg, an assistant of Liebig’s, performed the analytic work. The 
patient died (in coma) in 1869, shortly after exhibiting symptoms of alcoholic 
intoxication, but before the reactions of the substances chiefly concerned were 
as well known as they are now; and incipient diabetic coma may sometimes 
resemble alcoholic intoxication. 

The diabetic patient using an abundance of animal food ingests a 
large amount of salts. Lean meat contains about 0.70 per cent, 
of phosphoric acid, and diabetic pliospliaturia may be four times as 
marked as the normal phosphaturia. Whatever future researches 
may have to add to our present views on the functions and influence 
of mineral salts in the organism, the question that chiefly interests 
us here is whether or not the component salts of the bones are found 
in the urine in cases of severe diabetes in larger quantities than can 
be explained by the quantity of salts ingested plus the protoplasmic 
disintegration of the soft cellular tissues almost universally admitted 
as taking place in such cases. Calcium and magnesium phosphate 


METABOLISM AND NUTRITIVE NEEDS. 


23I 


and the other salts that enter into the constitution of the bones are 
excreted in such large amounts in some cases of severe diabetes 
that many writers in explanation suggest the existence of osteo¬ 
malacia as a result either of the acidosis or of trophoneurotic influ¬ 
ences. The question has not yet been decided, and Dr. E. Ten- 
baum’s recent researches only prove what an enormous amount of 
elaborate work will be required for its solution. 

The water streaming constantly through the organism, with most 
important functions and effects (of which there is yet much to learn), 
is generally increased in cases of diabetes. Even normally the figures 
are large. About sixty-three per cent, of the human body consists 
of water. A man of ordinary size ingests about 2.5 or 3 liters 
daily,* and excretes an equal amount. About one-third of the 
whole excretion passes through the lungs and the skin, and the 
greater part of the remainder is eliminated with the excreta and 
feces, chiefly in the urine, and only a comparatively small part 
in other excretions. In cases of diabetes the increased ingestion of 
water causes chiefly an increase in the amount of urine. The elimi¬ 
nation through lungs and the skin is usually diminished, partly on 
account of atrophy of the latter, partly on account of the increased 
amount of sugar in the blood, which retains the water more firmly 
than normally. 

Ever since 1580 some persons, in their amazement at the enormous quantity 
of urine sometimes passed in cases of diabetes, have held the curious notion that 
a diabetic patient may pass more urine than he ingests water, and even Gath- 
gens, in 1886, believed that he had proved this astounding fact, which could 
scarcely be explained otherwise than upon the theory that a diabetic patient, 
like concentrated sulphuric acid, attracts to himself the water in the air. This 
would have to be done by the so-called “ negative insensible perspiration ”—one 
of the most amusing products of speculative science. [The positive insensible 
perspiration is obtained by weighing a person at the beginning and at the end 
of the experiment, by adding the weight of the ingested water to the first and 
of the excreted water to the last figure; the difference between the two sums 
then represents the “insensible perspiration.’’] Burger, Nasse, Kiilz, and 
Engelmann have put an end to all these fanciful theories by showing that 
during somewhat extended periods no more water is excreted in cases of dia¬ 
betes than is ingested. The insensible perspiration in severe cases is undoubt¬ 
edly diminished. 


* According to Forster, from 2200 to 3500 cu. cm. 



232 DIABETES MELLITUS AND GLYCOSURIA. 

A diabetic needs in general the same amount of digested and 
utilized calories as a normal individual. This was proved by Pet- 
tenkofer and Voit,* and has been corroborated by Fr. Voit, Wein- 
traud, Pautz, Borchert and Finkelstein, and other investigators. 

According to Rubner, a normal man requires in twenty-four 
hours per kilogram of bodily weight : 

In repose,.32.9 calories.f With moderate work, . . . 41 calories. 

With light work,;): . . 34.9 “ With severe work, .... 48 “ 

The thin individual, richer in cells, requires more calories than 
the fat one, with more comparatively inactive adipose tissue. The 
growing child, with a larger bodily surface compared to its weight, 
requires more than a developed person. 

One gram of carbohydrate represents gross 4.1 calories, net 3.8.$ 

“ “ fat “ “ 9.3 “ “ 8.4. 

“ “ proteids “ “ 4.1 “ “ 3- 2< 

The figures for the gross value are Rubner’s, those for the net 
value are v. Rechenberg’s, who estimated the average loss from the 
amount of the ingested (but undigested) food in the feces. This 
loss usually is not greater in diabetics than in normal individuals, 
but it is probably somewhat smaller than it was in v. Rechenberg’s 
weavers, who doubtless received rather coarse food. 

The alcohol represents gross seven calories, and the net value 
may, in view of the small daily doses, be put practically at the same 


* The learned Professors Pettenkofer and Voit, however splendid their life’s work, 
unfortunately were sometimes a little absent-minded. Thus, when in 1867 they made 
their observations upon an unusually small diabetic Teuton, weighing only 54 kilograms, 
they at first overlooked the fact that he could not be expected to eat as much and to 
consume as much oxygen and produce as much carbonic acid as an ordinary Teuton ; 
and from the low figures they gained the impression that the metabolism was decreased. 
In relation to the bodily weight, however, their man consumed a perfectly normal 
amount of calories,—34.5 calories per kilogram of bodily weight in twenty-four hours, 
during repose, in the apparatus used. All subsequent figures, correctly interpreted, lead 
to the same result. (Livierato’s researches can not be considered satisfactory.) 

f I always mean great calories, viz., the amount of heat required to raise the temper¬ 
ature of one kilogram of water 1 0 C. 

J Only mechanic (and chemic) work entails expenditure of force. Nature is too 
generous to charge us for our poor intellectual work. 


£ Rubner’s figures are : 

4.116 calories for.starch. 3.877 calories for.lactose. 

3.959 “ .... cane-sugar. 3.692 “ .glucose. 






METABOLISM AND NUTRITIVE NEEDS. 233 

\ 

figure. The levulose, an important alimentary item in cases of dia¬ 
betes, represents about 3.7 calories gross, and nearly as much net, 
the amount taken being almost entirely absorbed. 

It must be borne in mind that the isodynamic law is to be accepted 
with some reservation, and that different kinds of food are not inter¬ 
changeable with regard to the number of calories they represent. 
The same number of calories derived from carbohydrates are more 
efficient in protecting the proteids of the organism than the calories 
derived from fats, and the latter rank higher in this respect than the 
calories derived from alcohol. Then, it seems to me that diabetics, 
especially when subjected to rigorous restriction of carbohydrates, 

1 

sometimes, though unfortunately only for a short while, apart 
from the calories lost by glycosuria, consume an amazingly large 
amount of calories. I have seen the value utilized reach nearly one 
hundred calories per kilogram of bodily weight in twenty-four hours. 
The toxic disintegration of protoplasm in severe cases explains this 
phenomenon in part. In other part it may be explained by the 
increased work necessary for the mere transformation of other 
molecular structures into glucose. Still, I do not feel at all certain 
that we know at present in every detail how to estimate dietic 
values for our diabetic patients. 

To estimate the caloric value of a patient’s food we must weigh 
all that he ingests and obtain the net value of the total. So far as 
proteids are concerned, we can take the easier way of determining 
the nitrogen in the urine. Albumin consisting of sixteen per cent, 
nitrogen, the ingested and digested albumin can be determined in 
grams by multiplying the number of grams of nitrogen in the urine 
by ^-g- 0 (= 6.25). (We then presume that practically all of the 
nitrogen has, as usual, been ingested in the form of proteids, and we 
take no account of the toxic disintegration of the tissues, which is a 
feature only of severe cases, and usually gives rise to the ap¬ 
pearance of comparatively small amounts of nitrogen in the urine, 
and which can not be determined without an immense amount of 
analytic work.) In using this mode of calculation we must, of 
course, value each gram of proteid at 4.1 calories. From the final 
sum of calories derived from proteids, fats, carbohydrates, and 
alcohol we then subtract the number of calories lost in the urine in 
the form of glucose, valued at 3.7 calories per gram. 

16 


234 


DIABETES MELLITUS AND GLYCOSURIA. 


Mr. R. has drunk 0.5 liter of milk with 17.5 grams of proteid, 18 grams of 
fat, and 24 grams of lactose ; which represent in calories 17.5 X 3*2 -f 18 X 
8.4 -f- 24 X 3-8 = 298.4. He had had 650 grams of raw meat, with about 20 
per cent, of proteids and 6.5 per cent, of fats and a net value of 416 + 354-9 
= 770.9 calories. Four eggs may be considered as representing 280 calories. 
Two hundred grams of butter (with 1.6 grams of proteid, 166 grams of fat, and 
0.4 grams of carbohydrate) represent 1394.6 calories ; 100 grams of rye-bread, 
209.84 calories; 50 grams of rich cheese yielded 13 grams of proteids + 15 
grams of fat -(- 1.25 grams of carbohydrate = 172.2 calories. Sixty grams of 
American whisky represent about 219 calories. No account was taken of some 
tomatoes and some “ sauerkraut.” If I am correct in my calculations—and of 
this I am not certain—R. received 298.4 -f- 770.9 -f- 280 -f- 1304.6 -j- 209.84 + 
172.3 -f- 219 = 3345. Mr. R., again, lost 51.8 calories in 14 grams of glucose 
in the urine, and thus really received only 3263.2— i. e ., a trifle more than 40.3 
calories per kilogram of his bodily weight, which was 82 and was increasing. 

Mr. L. had excreted 31 grams of nitrogen, and had thus utilized 62.5 X 31 
— 193.75 grams of proteid, or 4.1 X 193-75 = 793-3 calories. About 180 
grams of fat had yielded, net, 1512 calories. Ninety grams of white bread had 
yielded 179.18 calories. Twenty grams of alcohol had yielded 140 calories. 
The man had lost 32 grams of glucose, or 118.4 calories. He had thus utilized 
2624.48— 118.4 — 2506.08 calories. He weighed 68 kilograms, had received 
over 36.8 per kilogram, did not perform much work, and increased in weight. 


These calculations, however, are troublesome, and will not be 
undertaken in addition to the strain of practical work. It is easy, 
however, to remember that soft, white bread usually yields about 
twice as many calories as its own weight in grams ; that an egg 
represents about 70 or 75 calories; that raw, lean meat yields a 
somewhat larger, raw, lean fish a somewhat smaller, number of 
calories than its own weight in grams ; that butter yields about 7 
calories per gram, and alcohol also 7 calories per gram. All of 
these figures represent the net value, and are all that the prac¬ 
titioner need bear in mind when confronted with the important task 
of informing his patient as to the necessary amount of food to be 
ingested. 

The oxygen consumed and the carbonic acid generated in cases 
of diabetes equal normal quantities. Except what is represented by 
the glucose in his urine and by diabetic toxins, the diabetic patient 
oxidizes his food, especially the sometimes enormous quantities of 
fat, as a normal person does, just as he oxidizes organic acids 
(Strauss), or lactates (Weintraud), or benzol (v. Nencki and Sieber), 
etc. The normal consumption of oxygen varies from 3 to 4.5 


METABOLISM AND NUTRITIVE NEEDS. 


235 


cu. cm., and is, on the average, 3.81 cu. cm. per kilogram of bodily 
weight in the minute. The amount of carbonic acid excreted, esti¬ 
mated on the same basis, varies from 2.5 to 3.5 cu. cm., and is, on 
the average, 3.08 cu. cm. The figures that Leo * and others have 
found in cases of diabetes correspond exactly with these figures. 

Since Reignault’s and Reiset’s classic researches it has been known 
that the relation between the oxygen consumed and the carbonic 
acid excreted varies somewhat, for evident chemic reasons, ac¬ 
cording to the nature of the food, so that the respiratory quotient, 
or consumed^ 2 * durin g the ingestion of food consisting essentially of 
carbohydrates approaches the quantity 1. If proteids make up the 
greater part of the food, the figure is about 0.73. When large quan¬ 
tities of fat exclusively are taken, the quotient falls somewhat, and is 
about o./o.f It is evident that the quotient in diabetes approaches 
in general the latter values, the patient not being able fully to 
utilize the digested carbohydrates, J and that it is the farther from 
the ordinary maximum value of 1 the less carbohydrate oxidized, 
whether this arises from restriction of supply or from a low limit of 
the power of assimilation. Laves’ and Weintraud’s researches show, 
however, that a diabetic patient on an exclusive diet of meat and fat 
has the same respiratory quotient as a normal person on the same 


* “ Zeitschr. f. klin. Med.,” Berlin, 1891, Supplement. 

f Laulanie found that in starvation both the respiratory quotient and the production of 
heat are at their lowest. With an exclusive supply of meat (muscles) both the produc¬ 
tion of heat and the respiratory quotient increase. Both figures in the latter become 
higher, but the increase in the amount of carbonic acid excreted is rather greater than 
that of the oxygen excreted. The quotient, however, still remains comparatively small. 
With an almost exclusive supply of carbohydrates the quotient increases considerably and 
may exceed the figure I. The thermic curve follows the curve of the absorption of 
oxygen. A considerable part of the carbonic acid is produced without the generation of 
heat by the transformation of carbohydrate into fat. 

\ Laves and Weintraud, from the results of their investigations, have reached the 
conclusions that in cases of diabetes the ingested carbohydrates, even apart from what 
is lost as glucose in the urine, do not give rise to the production of fully as much car¬ 
bonic acid as in normal individuals, probably because a larger part of the carbohydrates 
remains in cases of diabetes at a lower point of oxidation ; e. g ., as oxalic acid instead of 
forming water and carbonic acid. 

Iienriot, Magnus-Levy, and Bleibtreu also found that with an abundant and exclusive 
supply of carbohydrates the amount of carbonic acid excreted may attain a higher figure 
than the amount of oxygen consumed, so that the respiratory quotient exceeds the figure 
I, and may even reach 1.3. 




236 


DIABETES MELLITUS AND GLYCOSURIA. 


diet, and Leo’s figures of this quotient make it evident that even in 
very severe cases of diabetes with a mixed diet a part of the carbo¬ 
hydrates must have been utilized and then excreted as carbonic 
acid. 


CHAPTER VIII.—INVESTIGATION OF A CASE OF DIABETES. 

It is the duty of every physician to test his patient’s urine for 
sugar. This investigation alone enables us to detect a simple, but 
rarely insignificant, habitual glycosuria, and the presence of sugar 
in the urine may be the one distinctive symptom of a mild but true 
diabetes. 

In making this test two most important points must be observed. 
In testing there should be used, systematically, a sample of the 
urine likely to contain the maximum, or nearly the maximum, per¬ 
centage of sugar excreted during the twenty-four hours, and the 
test should be so performed as to reveal the minimum distinctly 
pathologic quantity of glucose in the urine. 

There are, as we have seen, a great many individuals with a 
lowered power of assimilating carbohydrates who secrete glucose 
only for short periods in the day, some time after meals, and then 
only in small quantities. Even true diabetics in the mild stage are 
often, even apart from diet, free from glycosuria for some parts of 
the twenty-four hours, especially in the morning before the first 
meal. 

The first and most important ride is, therefore, never to use for 
a test a specimen of urine passed when the patient's stomach is 
empty, before the first meal of the day. 

The best means of deciding from a single examination of the urine 
whether a person is normal or not in this respect is furnished by a 
sample passed an hour after the end of the dinner. In cases of sim¬ 
ple glycosuria the excretion at this time is, with rare exceptions, 
near its maximum. The bladder should be emptied just before the 
meal, which ought to be a mixed and abundant one, including 



INVESTIGATION OF A CASE OF DIABETES. 


237 


meat, fat, bread, potatoes, rice, and sweets, but not any consider¬ 
able quantity of alcoholic liquors. 

The patient must be in his ordinary state ; the sample of urine 
ought not to be taken during any illness or indisposition or after 
violent emotion or excess of any kind. 

For the purpose of revealing with certainty the presence of patho¬ 
logic traces of glucose, the practitioner will do well to use con¬ 
stantly two different reduction-tests, and to verify the saccharine 
nature of the reducing-substance by the fermentation-test whenever 
doubt exists. The best reagents known for this purpose are Ny- 
lander’s solution of bismuth and Trommer’s test, used in a some¬ 
what modified way with Fehling’s solution of copper.* 

The test with Nylander’s solution is the easiest to perform and 
to observe. A tube is filled one-fourth or one-third with urine, and 
one-tenth or one-fifth as much of Nylander’s solution is added, the 
mixture being boiled for four or five minutes. It is important to boil 
for the full length of time. Under these conditions urine containing 
at least some tenths of a per cent, of glucose will be rendered more 
or less opaque and black ; urine containing only 0.02 or 0.03 per 
cent, will assume a somewhat brownish color, in consequence of 
admixture of the reduced bismuth with the flakes of phosphates, 
etc. Urine containing no sugar, or less than 0.02 per cent., will, 
except in rare cases, maintain its transparency and its yellow color ; f 
the latter will perhaps be somewhat deepened. 

Trommer’s test, as is known, has undergone many modifications, 
and may be performed in 'several different ways. I have adopted 
Worm-Muller’s modification in part, and like to combine it with the 
decoloration of the urine by filtering it through well-pulverized and 


* Both of these tests are much easier and quicker of performance’than Fischer’s test, 
and are, when only hundredths of a per cent, of glucose are concerned, at least as re¬ 
liable. Fischer’s test, as is well known, consists in heating (over a water-bath) for about 
half an hour about fifty parts of urine, to which have been added one part of phenyl- 
hydrazin chlorate and two parts of sodium acetate; the characteristic yellow crystals ot 
glycosazone form in cooling. Even when pure phenylhydrazin is used the test—which 
also yields similar crystals with other saccharids than glucose—yields, when 0.02 per cent, 
or smaller quantities of glucose are present, imperfect crystals, not with certainty to be 
distinguished from similar formations due to pentoses (E. Holmgren) or glycuronic acids 
(except by their melting at 205 0 C.—401° F.) (Thierfelder, Geyer). 

■[•Apart from the white flakes of the phosphates. 



238 DIABETES MELLITUS AND GLYCOSURIA. 

well-washed animal charcoal. In one tube I put a few cubic centi¬ 
meters of the urine and in another about the same amount of Feh- 
ling’s solution. The latter is then diluted with two or three times 
its volume of water, and the contents of both tubes are simulta¬ 
neously heated to boiling. As soon as they are fairly boiling I let 
them cool for twenty-five seconds, the temperature fallingto 70° or 
75° C. (158° or 167° F.).* I then slowly pour the urine into the 
other tube ; reduction will take place within five or ten minutes if the 
urine contain at least 0.01 or 0.02 per cent, of glucose. By following 
Worm-Muller’s directions closely, and especially by determining 
experimentally the best possible quantitative relations between 
the solution and the urine, one may somewhat improve the test, 
which, however, performed in the manner just described, is delicate 
enough for practical purposes and consumes but a short time. 

I sometimes perform the test by passing not too small a quantity 
of urine through animal charcoal on the filter, then washing the 
charcoal with a small quantity of water, diluting one volume of 
Fehling’s solution with two or three volumes of this water, and 
heating to the boiling-point. 

In whatever manner the reduction-test is performed, it is absolutely 
necessary, in cases at all doubtful, to verify the saccharine quality 
of the reducing-substances by the fermentation-test. To this end a 
small piece of yeast is placed in a tube almost filled with urine, which 
is permitted to stand at ordinary room-temperature or in a some¬ 
what warmer place. If after fermentation the reducing-substance 
has disappeared or diminished, it may be concluded that it was glu¬ 
cose or levulose or maltose, of which saccharids glucose is very 
common in urine and the two others are extremely rare. 

By omitting the fermentation-test and by trusting only to reduction-tests, 
one incurs great danger of increasing, in his own mind or in the literature, the 
large number of cases of false glycosurias. 

Referring for further particulars to the special manuals, I would here only 

* Worm-Muller found that though the sugar reduces more readily at a higher temper¬ 
ature than 70° or 75 0 C. (158° or 167° F.), a reduction at this higher temperature is 
easily brought about by other substances than glucose. At a lower temperature than 70° 
C. (158° F.) the test is less delicate. 

The decoloration of the urine, which was first practised by Claude Bernard, was 
adopted by Seegen as a modification of Trommer’s test, for the purpose of eliminating 
the reducing uric acid and substances that prevent the cupric oxid from being precipitated. 



INVESTIGATION OF A CASE OF DIABETES. 


239 


I 

recapitulate that glucose reduces Fehling’s, Nylander’s, and Barfoed’s * solu¬ 
tions, turns the ray of polarized light to the right, and is readily and completely 
decomposed into alcohol, carbonic acid, etc., by the influence of common yeast 
and of saccharomyces apiculatus. Its crystals of osazone melt at 205° C. 
(401° F.). 

Uric acid and kreatinin, which are present normally and constantly in the 
urine, cause reduction, but do not undergo fermentation. 

Many of the combined glycuronic acids, some of which are present in 
normal urine (in combination with indoxyl, skatoxyl, phenol, etc.), also 
cause reduction. After the ingestion of chloral there may, with or without 
glucose, be quite a considerable reduction from the presence of urochloral 
acid (= trichlorethyl-glycuronic acid). The combined glycuronic acids do not 
undergo fermentation, and turn the ray of polarized light to the left.f One 
may remove the combined glycuronic acids from the urine with ammonia and 
lead-acetate. 

Many substances besides may be responsible for the presence in the urine 
of nonsaccharine reducing-substances, some of which probably are combined 
glycuronic acids. Other substances, such as benzoic, salicylic, oxalic, prussic, 
and mineral acids, turpentine, different phenols, morphium, copaiba, glycerin, 
kairin, sulphonal, trional, arsenic, caustic alkali, etc., may cause true glyco¬ 
suria. Rhubarb, senna, eucalyptus, large doses of quinin, also cause a reaction 
with Nylander’s solution similar to that caused by glucose. 

Alkapton reduces Fehling’s solution, but not the solution of bismuth. It 
does not deflect the ray of polarized light, and it does not undergo fermenta¬ 
tion. Urine containing alkapton presents, after some time, a brown, almost a 
black, color. 

The disaccharid maltose, which probably sometimes occurs in urine, is, 
like glucose, attacked by common yeast; but it reduces Fehling’s solution only 
two-thirds as much as glucose, and it turns the polarized light three times as 
much to the right. Unlike glucose, maltose does not reduce Barfoed’s solution, 
which is, however, reduced to some extent by other substances present in all 
urine. 

Levulose causes about as much reduction as glucose, and is quite readily 
attacked by common yeast; but it turns the ray of polarized light to the left, and 
its osazone melts at 190° C. (374° F.). 

Lactose turns the ray of polarized light to the right and reduces Nylander’s 
and Fehling’s solutions. It does not reduce Barfoed’s solution, which, 
unfortunately, with regard to urine, does not help us much, as other sub¬ 
stances (than saccharids), that are constantly present in urine, cause its reduc¬ 
tion ; but lactose, though it undergoes lactic-acid fermentation or alcoholic 
fermentation with other fungi, does not ferment at all with saccharomyces 
apiculatus, and ferments with common yeast only when it has been inverted 
into its two monosaccharids, glucose and galactose, which both ferment. 


* Barfoed’s solution is a solution of from 0.5 to 4 per cent, copper-acetate with one 
per cent, of free acetic acid. It is not reduced by lactose or maltose. 

f Glycuronic acid per se turns the ray to the right, but it is never present in urine. 





240 


DIABETES MELLITUS AND GLYCOSURIA. 


« 

The inversion is likely to take place spontaneously after some time. Lactosa- 
zone melts at 200° C. (392 0 F.). 

Galactose is not under ordinary circumstances to be expected in urine, but 
may be present after the ingestion of large amounts of galactose, and arises 
(with glucose) when lactose is boiled with diluted mineral acids. It reduces 
somewhat less, but turns the ray of polarized light more strongly to the right 
than glucose. Its osazone melts at 193 0 C. (379 0 F.). Laios (found by Leo in 
1887) reduces, but does not ferment. 

Pentoses reduce, but do not deflect the ray of polarized light and do not fer¬ 
ment. They are found both in diabetic and in normal urine. 

The substance found in urine after the ingestion of turpentine reduces and 
ferments, but it does not deflect the ray of polarized light (Vetlesen). 

Animal gum turns the ray of polarized light to the right, but does not fer¬ 
ment. It forms a compound with the copper of Fehling’s solution, which is pre¬ 
cipitated in whitish-blue flakes. 

If after a generous mixed meal the urine contains no glucose as 
determined by the tests named, a distinctly pathologic deficiency in 
the power of assimilation is excluded. 

Some who have occupied themselves a good deal with similar researches 
may feel some doubt as to the correctness of this assertion. May not, 
they will probably urge, a simple glycosuria, or even a “periodic” or an 
“ alternating” diabetes, or a very mild common diabetes after abstinence from 
carbohydrates continued for some time,|withstand such a trial without the ap¬ 
pearance of glucose in the urine ? To this I would answer that even in such 
cases the urine will, an hour after a generous mixed meal, yield to the tests 
named evidence of the presence of at least a trace of glucose. I have found 
this to be the case even in individuals who have been capable of taking large 
portions of rice or cane-sugar without the development of glycosuria. Escape 
from detection in any stage of the glycosuric dystrophy under the circumstances 
named will at all events be exceedingly rare. 

If after a generous mixed meal the urine contains a considerable 
quantity (several per cent.) of sugar, the secretion is undoubtedly 
that of a diabetic individual. 

My next step—never to be omitted—will then be to submit the 
urine to Gerhardt’s test for diacetic acid. This is done in a moment. 
I almost fill an ordinary test-tube with urine and add six or eight 
drops of a solution of ferric chlorid. If the urine, with the patient 
in his customary state and with a good supply of calories in his food, 
turns a red, or, still more, if it turns a dark bluish-red color, the 
patient is, without doubt, in the severe stage of diabetes. It is then 
unnecessary, and, besides, it would incur danger of coma, to exclude 
carbohydrates from the patient’s food. 


INVESTIGATION OF A CASE OF DIABETES. 24 1 

If Gerhardt’s reaction is wanting or indistinct, I may, without 
danger, so far as possible exclude carbohydrates from the diet for 
several days or a couple of weeks. If during this regime the urine 
becomes free from glucose, the patient is in the mild stage ; but if 
sugar appears, he has entered upon the severe stage of diabetes. 

Having ascertained that the patient is in the mild stage of dia¬ 
betes, it must be determined how much carbohydrate he is capable 
of taking without the development of glycosuria. For practical 
purposes this is best done by allowing the patient, in addition to 
generous animal food, a certain amount of the kind of bread that he 
prefers. In doing this I may either, after absolute exclusion of 
bread, permit larger and larger amounts until glycosuria appears, 
or diminish the amount after a more generous supply until the gly¬ 
cosuria ceases; and it is not an entirely indifferent matter which of 
these plans I select. With exclusion of carbohydrates or restriction 
of them below his power of assimilation the patient increases this 
power, and thus, by progressing from small to larger amounts, I may 
find a higher power of assimilation than by pursuing the opposite 
course. If I am anxious in a case not to give the patient more car¬ 
bohydrates than he can take continually without the development 
of glycosuria, I proceed from amounts of carbohydrate that are 
beyond his power of assimilation, and decrease them until glyco¬ 
suria disappears. In either event I use for analytical purposes 
samples from the whole amount of urine collected during twenty- 
four hours. 

If after a generous mixed meal I find only a small quantity of 
glucose in the urine, I must submit the case to further investiga¬ 
tion before giving the dystrophy a name or forming a concrete 
opinion as to its nature. In this case, too, I always take for 
analysis a sample of the urine collected and measured during 
twenty-four hours, while the patient consumes with his daily food 
a rather large, determined amount of carbohydrates, represented by 
from 1 50 to 200 grams of bread and some potatoes, rice, macaroni, 
peas, and cane-sugar. The patient should observe this regime for 
a few days before collecting his urine for the test. If under such 
circumstances, and with the patient in his habitual state, the mixed 
urine for twenty-four hours contains a determinable amount of glu¬ 
cose, amounting at least to several tenths of a per cent., the case is 


242 


DIABETES MELLITUS AND GLYCOSURIA. 


one of true, though it may be very mild, diabetes, and I am then 
generally able to find other purely diabetic symptoms besides 
glycosuria. 

If an individual excretes for a short time after every generous 
mixed meal a determinable quantity of glucose, which in the urine 
passed at that time may occasionally reach perhaps even one per 
cent, or somewhat more, but which, in the whole amount of urine for 
the twenty-four hours, during a continued, abundant supply of carbo¬ 
hydrates, is present in scarcely more than traces, or, at all events, in 
less than several tenths of a per cent., the decision as to whether 
the case shall be called one of simple glycosuria or of light dia¬ 
betes is to a certain extent a matter of opinion. 

Still, continued investigation will elicit further information as to 
the patient’s state and future prospects. 

The patient, therefore, may be given, one morning for breakfast, 
exclusively, a large portion— e. g ., 200 grams—of dry rice, well 
cooked in milk or water. The urine is then collected for six or 
eight hours. Even in cases in which, after every generous mixed 
meal, glycosuria appears, the urine, after such an amount of rice, 
may remain perfectly free from glucose. I am then inclined to call 
the case one of simple glycosuria, which, especially in middle or 
advanced age, generally is of no noteworthy clinical importance. 
A recurring glycosuria after meals consisting exclusively of rice or 
bread, has, on the other hand, a deeper significance than the same 
phenomenon after generous mixed meals or after the ingestion of 
large amounts of cane-sugar, and I consider the designation diabe¬ 
tes in such a case better to represent the clinical condition and the 
prognostic aspect than that of simple glycosuria. 

If after the ingestion of large quantities of rice the patient exhibits 
no glycosuria, I give him on another day 200 or 300 grams of cane- 
sugar, which is most easily taken dissolved in some mineral water 
containing free carbonic acid. An individual who, after the ingestion 
of large amounts of boiled rice, excretes glucose with his urine will 
also do so after the ingestion of large amounts of cane-sugar. It is 
quite possible, however, that a person in whom, after every dinner 
of mixed food, glycosuria appears may exhibit none after the in¬ 
gestion of large amounts of cane-sugar, but only excrete some un¬ 
changed saccharose, as everybody without exception does under 


INVESTIGATION OF A CASE OF DIABETES. 


243 


the circumstances. In such a case the urine will not reduce Feh- 
ling s and Nylander’s solutions before but only after being boiled 
with several drops of sulphuric acid. I then call the case one of 
simple glycosuria. In other cases the ingestion of a like amount of 
cane-sugar will be followed by the appearance in the urine of a mix¬ 
ture of cane-sugar and glucose, and I find more marked reduction 
after boiling with sulphuric acid than before, the difference rep¬ 
resenting the amount of cane-sugar that had passed through the 
organism unchanged.* Such a case always represents a weakened 
power of assimilation, and is either one of simple glycosuria or of 
diabetes. Referring to chapter 11 of this book, I am the more in¬ 
clined to the milder name and the more favorable prognosis, the 
more unchanged cane-sugar and the less glucose the patient ex¬ 
cretes. 

It is also possible to test the power of assimilation by the administration of 
a large amount of glucose ; only as all persons excrete glucose after the inges¬ 
tion of very large amounts of this saccharid, the necessary quantity of which 
varies greatly even in the same individual under apparently similar conditions, 
and as under ordinary conditions such amounts of glucose are never taken, I 
prefer the other tests. From my own researches I will say that the develop¬ 
ment of glycosuria after the ingestion of 100 grams of glucose often denotes a 
weakened power of assimilation. In using ordinary “technical” glucose, 
mixed with dextrin, one ought to put the test-amount at least at 150 grams. 
Achard and Weil (1898) inject 10 cu. cm. of pure glucose subcutaneously , and 
consider the appearance of glycosuria after this pathologic. In a normal 
person, whose bodily weight unfortunately is not mentioned, Fritz Voit found 
(1896), after the subcutaneous injection of sixty grams of glucose, a trace of 
sugar in the urine ; 100 grams given in the same manner caused a glycosuria of 
2.6 grams. (Biedl, R. Kraus, and Pavy have made similar researches. If made 
in large numbers under different dietetic conditions, and with a determination of 
the bodily weight, experiments with subcutaneous injections may provide the 
means of finding some exact expression for the normal power of assimilation.) 
To decide immediately and after a single investigation the nature and the 
prognosis of a slight excretion of sugar, is, as may be understood from the 
foregoing, quite impossible. Neither does there at present exist any universal 
rule for the refusal or acceptance of an application for life-insurance in these 


* By boiling with diluted sulphuric acid the cane-sugar is “ inverted ” into a mixture of 
glucose and levulose. The former turning the ray of polarized light to the right, the 
latter to the left, polarization yields no information. Both saccharids, however, cause 
practically equal reduction (levulose j 9 ^ 4 ^ as much as glucose), and titration before and 
after boiling yields information as to the amount of glucose and the amount of cane- 
sugar excreted. 



244 


DIABETES MELLITUS AND GLYCOSURIA. 


cases, and the physicians of insurance companies often decide the fate of such 
applications in a most summary way. Some examiners perform the analysis 
in the morning, when the patient’s stomach contains no food, or without any 
information as to his diet. In this way many a diabetic in the mild stage 
secures life-insurance. On other occasions applications are refused on account 
of a slight and accidental excretion of sugar. The most rational manner of 
reaching a decision from a single investigation is, perhaps, to have the appli¬ 
cant partake of a large amount of rice with cane-sugar, and two hours afterward 
pass his urine for analysis. If such a specimen yields no distinct reaction for 
sugar, there is no reason, on a diabetic basis, for refusing the insurance; if the 
urine contains a slight amount of glucose, the insurance ought to be refused 
until more careful investigation shall settle the question as between simple 
glycosuria or mild diabetes, when insurance should be refused in the latter and 
accorded on higher premiums in the former case. Even with this test many 
persons who habitually excrete sugar after mixed meals would be accepted as 
first-class risks, and the same might happen in rare instances of true diabetes 
after prolonged abstinence from carbohydrates. It is perhaps possible to 
decide diagnostic questions quickly by Bremer’s new tests, which are described 
immediately below, but which I have not yet had time to study. 

Dr. Ludwig Bremer,* of St. Louis, has made the interesting and 
important discovery that diabetic blood (to the naked eye) and its 
red blood-corpuscles (microscopically) are colored differently from 
normal blood by certain dyes, whether there is or is not for the 
moment sufficient hyperglycemia to induce glycosuria. It is as yet 
not known at what stage in the development of glycosuric dystro¬ 
phy this peculiarity of the blood first appears, but some of Bremer’s 
cases were instances of glycosuria (according to his views f), and it 
seems that we have in this method a means also of detecting the 
glycosuric dystrophy in its incipiency. 

Equal parts of saturated watery solutions of methylene-blue and 
eosin are mixed, and the precipitate that forms, and which is insoluble 


*“ New York Med. Jour.,” 1896. 

f Dr. Bremer’s views on other subjects differ widely from my own and from those 
held by most students of diabetes. When Dr. Bremer says : “ It is a well-known fact 
that by means of dieting, and by the administration of certain drugs (antipyrin, calo¬ 
mel, and ammonium carbonate), the sugar can be made to temporarily greatly diminish 
or entirely disappear from the urine, even in cases of well-established and undoubted 
diabetes,” or that “ fasting is a tolerably certain means of freeing the urine from 
sugar,” I can scarcely approve of his expressions, nor do I share his opinions. I do 
admit, however, that Dr. Bremer deserves great credit for his important discovery, which 
in some cases probably will constitute a valuable diagnostic means, and which may lead 
to a better knowledge of the diabetic changes in the red blood-corpuscles. 



INVESTIGATION OF A CASE OF DIABETES. 245 

in water, but soluble in alcohol, is washed and dried on a filter. To 
this powder some methylene-blue (usually about one-sixth by weight) 
and some eosin (about one twenty-fourth by weight) are added. 
The whole forms a powder of reddish-brown color. Every time the 
test is to be made a fresh test-solution is to be prepared by dissolv¬ 
ing from 0.025 to 0.05 gram of this powder in about io grams of 
dilute alcohol (1:3). A drop of blood from the finger of the 
patient is spread between two cover-glasses, which are then boiled 
over a water-bath for four minutes in equal parts of alcohol and 
ether, to fix the hemoglobin in the red blood-corpuscles, and trans¬ 
ferred to the staining solution described for about the same length 
of time. After washing the cover-glasses in water, normal blood 
appears reddish-violet, while glycosuric or diabetic blood presents 
a sap-green or sometimes a bluish-green color. 

In a later notice * Dr. Bremer has adopted a simpler method, 
spreading a drop of blood between the cover-glasses and exposing 
these for from six to ten minutes at a temperature of 13 5 0 C. 
(275 0 F.)—not below 129 0 C. (264.2° F.) nor above 140° C. (284° 
F.). The cover-slips are then placed for several minutes in a 
one per cent, solution of Congo-red or of methylene-blue, or 
Biebrich’s or Ehrlich-Biondi’s stain. The Congo-red colors dia¬ 
betic blood but faintly or not at all, while it gives normal blood 
a bright red hue. Methylene-blue, which gives normal blood a 
violet color, gives diabetic blood a faint greenish or yellowish- 
green color. Biebrich’s stain does not color normal blood, but 
makes diabetic blood a purple-red. Ehrlich-Biondi’s stain makes 
diabetic blood orange and normal blood violet. 

Dr. Williamson, of Manchester, with a capillary tube mixes 
twenty volumes of blood with forty volumes of water, forty vol¬ 
umes of a six per cent, solution of potassium hydrate, and one vol¬ 
ume of a solution of methylene-blue (1 : 6000), and keeps the whole 
in boiling water for five minutes. In the presence of normal blood 
the mixture remains blue and afterward becomes greenish, while 
with diabetic blood the mixture turns a pale yellow. 

Eoewy and others found Bremer’s and Williamson’s tests valuable 
even when the diabetic patient’s urine did not contain glucose. 


*“ New York Med. Jour.,” 1897. 






246 


DIABETES MELLITUS AND GLYCOSURIA. 


Patients, however, submit much more readily to examination of 
their urine than to examination of their blood, and these tests are 
little likely ever to come into general practice. It is, therefore, of 
great importance that Dr. Bremer (1897) has published a method of 
performing a color-test with the urine. A small quantity of a powder 
consisting of three parts of gentian-violet and two parts of eosin is 
introduced into a tube almost filled with urine. Even at ordinary 
temperature, but more quickly on application of heat, diabetic 
urine assumes a deep violet, almost blue color; normal urine, a 
brownish-red color. This reaction, which appears whether the 
diabetic urine contains glucose or not, is explained by the solution 
of gentian-violet in diabetic but not in normal urine. In persons 
with simple glycosuria, but living on the boundary-line of diabetes, 
the urine presents a combination of the two colors. 

I believe that these most interesting tests will, in combination 
with those hitherto employed, prove most valuable in cases of 
life-insurance and in cases of simulated diabetes (see below), and 
I intend, as soon as time permits, to devote a good deal of attention 
to Bremer’s tests. 

A medical practitioner’s knowledge of a diabetic patient’s urine 
must comprehend : 

1. The quantity \ 

2. The specific gravity I 

3. The quantity of glucose \ of the urine collected during twenty-four hours, 
upon a determined sup- V 

ply of carbohydrates / 

4. The absence or presence of Gerhardt’s reaction and, if possible, of / 3 -oxybutyric 
acid. 

5. The absence or presence of albumin and of— 

6. Structural elements from the kidneys. 

To obtain information with regard to the excretion of urine for the twenty- 
four hours, it is necessary expressly and most distinctly to instruct the patient 
that he must collect every drop of urine in one vessel from, e. g., 8 o’clock one 
morning until 8 o’clock the next morning. Any one but a physician would 
believe this task, or at least the full understanding of it, to be the easiest possi¬ 
ble. In this, however, as in everything else, we often find painful illustrations 
of the correctness of Billroth’s appropriate remark : In matters pertaining to 
the natural sciences the average man is quite stupid (“ ganz dumm ”). 

To take the specific gravity one must have at least two urometers, one 
graduated from 1.000 to 1.020, and another from 1.020 to 1.040. A specific 
gravity above 1.040 is rare. The fourth decimal must generally be taken 


INVESTIGATION OF A CASE OF DIABETES. 247 

without any corresponding gradation on the urometer, which rarely is graduated 
to more than three decimals. 

A practitioner who does not observe many diabetic patients generally pos¬ 
sesses no polarimeter, and finds reduction by Fehling’s solution (or like 
methods) too tedious a mode of determining the degree of glycosuria. For 
him Roberts’ method, based upon the difference in the specific gravity of the 
urine before and after complete fermentation, is the easiest and best for deter¬ 
mining the percentage of glucose present. A glass cylinder is almost filled 
with urine, the specific gravity taken to four decimals, about two grams of 
common yeast added, the yeast-cells somewhat evenly distributed through the 
liquid by stirring, and the cylinder, covered with a piece of glass, placed for 
fermentation if possible in a room with a temperature somewhat above the 
ordinary.* After two or three days it is ascertained with Nylander’s or Feh¬ 
ling’s solution that no determinable amount of glucose remains, and the 
specific gravity is again taken to four decimals. The latter figure is subtracted 
from that first obtained, and the difference is multiplied by a coefficient, which 
has been differently estimated and varies somewhat with the percentage of 
sugar, but which for practical purposes may, according to Lohnstein, be put at 
the constant 234. The results thus obtained scarcely differ from the correct 
ones by as much as 0.01 per cent., and they are sufficiently accurate for the 
purposes of the general practitioner. Thus : 

Specific gravity before fermentation was 1.0345, and the 
“ “ after “ “ 1.0165; the 

Percentage of sugar is 0.0180 X 2 34 = 4-86. 

Finally, I must again emphasize the necessity of performing Gerhardt’s test, 
the easiest, the most important, and the most neglected of all. Into an ordinary 
test-tube nearly filled with urine, six, eight, or ten drops of a solution of ferric 
chlorid are poured; a red or a dark bluish-red color denotes the presence 
of diacetic acid. There is no method of quickly ascertaining the quantity. 
Oppler, of Breslau, adds the solution of ferric chlorid until the maximum in¬ 
tensity of color is reached ; he then adds diluted hydrochloric acid until the 
color again disappears. From the quantity of hydrochloric acid necessary for 
this purpose an idea is gained as to the quantity of diacetic acid. 

The practitioner who does not use a polarizing instrument can not determine 
the presence or the quantity of /3-oxybutyric acid, which permits him to form a 
distinct opinion with regard to the danger of coma. There are some points 
apart from this best mode of estimating such a danger that it is important to 
observe. If the reaction with six or eight or ten drops of a solution of ferric 
chlorid in a test-tube almost filled with the patient’s urine does not yield a true 
red, but only a brownish color, there is no considerable amount of /Foxybutyric 
acid present either in the urine or in the blood. If a distinct, but not pro¬ 
nounced, Gerhardt’s reaction with a light red color appears, the amount of 


* The specific gravity of urine sinks about 0.001 with every increase of temperature of 
3 0 C. (5.4 0 F.). To obviate the necessity of corrections and to avoid possible errors, it 
is best to determine the specific gravity in both instances at the same temperature. 




248 


DIABETES MELLITUS AND GLYCOSURIA. 


/Toxybutyric acid present is not large, and, unless the patient’s general state is 
very miserable, there will scarcely be any danger of coma. If the solution of 
ferric chlorid yields a deep, dark bluish-red, there is good reason to suspect the 
presence of a larger quantity of / 3 -oxybutyric acid. The degree of danger of 
coma in such cases depends in large part upon the patient’s general state. As 
has been already mentioned, one patient may go on for months excreting in 
the twenty-four hours many times as much /J-oxybutyric acid as is excreted by 
another patient for only a short time before the fatal degree of poisoning is 
reached. 

By the use of a polarimeter the task is much facilitated. After precipitating 
with ammonia and lead-acetate a sample of the mixed urine collected during 
twenty-four hours, and waiting for some time until the urine passes perfectly 
clear through the filter, the number of grams of the acid excreted in the twenty- 
four hours is easily determined by introducing the degree of levogyration into 
the formula, with the necessary correction for the dilution of the urine. As 
soon as this number reaches more than twenty in an adult, the “acidosis,” 
operating in combination with a low state of general health, may threaten 
coma. 

To demonstrate the presence of albumin there is no easier test than pouring 
nitric acid into a test-tube with a pipet beneath the urine. Even when only a 
trace of albumin is present, it then quickly shows as a thin, reddish-white layer 
immediately above the line of contact of the two liquids, below the less sharply 
defined, more grayish layer of urates, which often forms above it; care being 
taken when only one of the two layers is present not to mistake it for the other. 

The quantity of albumin, which generally is small and often below one- 
half in a thousand, is most practically and enough accurately determined by 
means of Esbach’s albuminimeter. 

With the aid of a centrifuge the task of finding casts of the renal tubules is 
much facilitated, care being taken not to permit hyaline casts to escape detection, 
and in cases of severe diabetes to keep a sharp lookout for the numerous small 
casts described by Kiilz. 

It is often worth the trouble to ascertain the patient’s capability of ingesting 
and digesting proteids by determining—usually by Kjeldahl’s method or by 
one of the many azotometers—the quantity of nitrogen excreted with the urine 
in twenty-four hours. By multiplying the number of grams of nitrogen by 6.25 
the number of digested grams of proteids is learned, not taking into considera¬ 
tion the nitrogen possibly ingested with other substances than proteids and the 
nitrogen derived from toxic, protoplasmic disintegration, both of which, in most 
cases, only form “ une quantite neglige able," and can not possibly be deter¬ 
mined by the physician. 

The general practitioner usually finding among his patients but a 
limited number of diabetics, as a rule does not, by analytic work, 
ascertain the changes in their nutritive state. On the other hand, 
he ought not to omit to follow these changes, even though in a 
somewhat crude but simple and practical manner. For this pur- 


INVESTIGATION OF A CASE OF DIABETES. 249 

pose he may use the scales, the patient being weighed once a month, 
or, if necessary, once a week. In doing this the patient must 
necessarily take his weight at the same time of day and in the 
same dress, or, if convenient, without any clothes at all. It is 
evident that even if this is done the varying contents of the bowels 
and the bladder may give rise to error. Further, a less important 
gain of fat may cover and conceal a more important loss of pro- 
teids. However crude this method of following the patient’s nutri¬ 
tive changes, it is of great practical importance, and, especially in 
two classes of cases, is not to be neglected by the conscientious 
physician. In severe cases it enables us to discover, and at once by 
all the means in our power to combat, any increase of the autoph- 
agy and rapid loss of weight, which often indicate the beginning 
of the end and the overwhelming danger of coma. In mild cases 
the scales enable us, during periods of marked restriction or exclu¬ 
sion of carbohydrates from the food, to control the loss of weight 
that usually occurs under such conditions, and which ought not to 
be too marked. A fat diabetic patient (in the mild stage) may— 
ceteris paribus —be permitted to lose more than a less fat patient, 
but no diabetic should be permitted to lose in a month more than a 
small percentage of his whole bodily weight. In the severe stage 
the physician should always do his best to prevent any loss of 
weight. 

The remaining part of the investigation in a case of diabetes occu¬ 
pies comparatively little time. I will cursorily mention the points 
that strike me as most important. 

In examining the patient as to his heredity one has especially to 
bear in mind diabetes mellitus and insipidus, gout, adiposity, and 
all neuroses (various forms of mental disease, neurasthenia, epi¬ 
lepsy, etc.), and exophthalmic goiter. In making inquiry as to 
mental diseases one must sometimes press the question in order 
to gain the necessary information ; an unintelligent, and sometimes 
even an intelligent, patient may, however, be irritated if the pres¬ 
sure be made too great. A satisfactory result is often more easily 
reached by asking as to symptoms rather than about names of 
diseases. 

With regard to the patient’s own life inquiry is made as to past 
diseases, especially gout, influenza, malaria, syphilis ; trauma, es- 

17 


250 


DIABETES MELLITUS AND GLYCOSURIA. 


pecially of the head ; excessive intellectual work ; powerful and 
permanent painful emotions ; sexual excesses, natural or unnatural; 
deprivations ; exposure ; indulgence in alcohol, tobacco, or other in¬ 
toxicants (morphin, cocain, chloral); gormandism ; overindulgence 
in sweets ; sedentary habits, etc. 

If the diabetes has been discovered and treated before my own 
investigation, I never omit to ask whether the discovery was made 
from the sudden appearance of diabetic symptoms (thirst, polyuria, 
etc.) or whether the disease has developed slowly and has been dis¬ 
covered accidentally (life-insurance, etc.) or in consequence of some 
chronic diabetic complication affecting the skin, the eyes, the teeth, 
etc. The prognosis, as has already been mentioned, is far better 
when the development is slow than when the onset is sudden. 

I likewise endeavor to secure information as to any loss of bodily 
weight, and attach much greater significance to this if it has begun 
before the diabetes was discovered and without any change of die¬ 
tetic regimen, than if it began after a restriction of carbohydrates, 
which, if carried to anything like an extreme, is likely to cause loss 
of flesh in any person, diabetic or not. 

I observe the patient’s general appearance, complexion, manner 
of moving and of talking. I never omit to examine the cavity of 
the mouth, which, from the existence of alveolar pyorrhea and 
decay or loss of teeth, may afford evidence of diabetes of long 
standing, or from the typical, diabetic “ crocodile ” tongue, and a 
strong smell of acetone on the breath may show that the disease 
has entered upon the severe stage. 

I first try to form an opinion as to the patient’s mental state by 
my own observation, and afterward, prudently— i. e. } as kindly, in¬ 
terestedly, and delicately as possible—put direct questions about 
central nervous symptoms, especially depression and irritability. I 
pay particular attention in my examination to neurasthenic symp¬ 
toms, whether revealed more directly through the nervous system 
or the organs of perception, circulation, digestion, and reproduc¬ 
tion : Depression ; irritability ; sleeplessness ; loss of memory or of 
capacity for intellectual work ; vertigo, spontaneous or from a great 
depth ; agoraphobia (rare) ; headache ; hyperesthetic, dysesthetic, 
or paresthetic sensations (casque neurasthenique , plaqtie sacree , and 
other rachialgic manifestations, formication, sense of heat or of cold, 


INVESTIGATION OF A CASE OF DIABETES. 2 $ I 

shooting, “ rheumatoid ” pains, neuralgia, migraine); neuromuscular 
asthenia; cramps in the calves ; neurasthenic asthenopia; hyper¬ 
esthetic, ocular, or auditory manifestations ; changes in taste and 
smell, etc. ; pseudoangina pectoris—increased frequency of pulse ; 
gastrointestinal disorders, with a capricious appetite ; nervous nausea 
or vomiting ; eructations, pains, flatulence (exceedingly common), 
sudden diarrheas, etc. ; sexual weakness and impotency. 

In cases of long standing or in cases complicated by gout I do 
not fail to look for symptoms of neuritis, and with a needle or a 
tube filled with hot water or the esthesimeter to test the sensibility, 
especially on the lower parts of the legs, where neuritic symptoms 
are more frequent and more intense. 

I test the knee-jerks (the prepatellar reflexes) a la Jendrassik. 
The patient reclines upon a chair with his eyes closed, his legs bent 
at the knee-joint at an angle of about no degrees, the feet some¬ 
what separated, and the whole sole on the floor. His hands are 
joined over his stomach, and he is told to relax the whole muscular 
system, especially the muscles of the legs, as much as possible. I 
place one hand near the knee, over the quadriceps femoris muscle, 
to feel the jerk, while with a small book in the other I try to elicit 
the reflex by striking a blow over the ligamentum patellae. I am 
thus able to perceive by touch better than by sight the slightest 
contraction of the quadriceps femoris. 

By physical investigation in the usual way I ascertain the size 
and the functional and valvular state of the heart, and I do not 
omit in forming an opinion as to this state to weigh the patient’s 
statement with regard to his capacity for climbing, or any other 
energetic muscular activity which increases the demands on the 
heart. Palpation of the radial artery discloses the frequency, 
rhythm, and strength of the pulse ; I try to detect any possible 
atheromatous rigidity of the radial, femoral, and temporal arteries. 

In examining the lungs I direct attention especially to ascertain¬ 
ing the absence or presence of any incipient or advanced changes in 
the upper lobes. 

I ask the patient about his appetite, the regularity of his bowels, 
etc. If there is any reason for presuming pancreatic disease, I 
request him to observe if the character of the stools indicates the 
presence of greater quantities of indigested fat than normal, and if 


252 


DIABETES MELLITUS AND GLYCOSURIA. 


this is the case, I give my own special attention to the subject. I 
determine the size, the consistency, and the sensitiveness of the 
liver. In deciding as to the existence of incipient cirrhosis of the 
liver I attach great importance to any enlargement of the spleen, 
and sacrifice some time in carefully ascertaining the size of this 
organ. I seek information with regard to the presence of any 
symptoms of gall-stones, which are not rare in cases of diabetes. 

I also inquire whether the patient has been troubled by pruritus 
or any local changes in the genitals. 

I direct special attention to the eyes and look chiefly for cataract, 
myopia, premature presbyopia, retinitis, and inflammation of the 
optic nerve. 

Simulation of diabetes is not rare in some European countries, and is 
generally attempted by persons who wish to secure exemption from military 
duty. 

To contrive the fraud, the simulator either (i) eats a large quantity of glucose, 
usually in honey, or (2) introduces some saccharid in his urine within or with¬ 
out the bladder, or (3) takes a dose of phloridzin or of phloretin. 

The ingestion of a large quantity of glucose is the shrewdest method. The 
consequent glycosuria, however, lasts only for a few hours, and then ceases 
when the supply is cut off. It is usually on the increase only for about an hour, 
and after this time the fraud can be discovered by giving a large portion of 
bread, and by observing that an hour later the glycosuria is on the wane instead 
of increasing. 

Fraud has sometimes been attempted by injecting a solution of some 
saccharid into the bladder or by adding some saccharid to the urine outside 
the bladder. (See the case of Abeles and Hoffmann.*) In the latter case the 
fraud is detected by letting the simulator pass his urine under observation, or 
by withdrawing it directly from the bladder. In both cases detection is gener¬ 
ally made easy by the simulator’s ignorance of the different kinds of saccharids. 
Women scarcely ever know of any other sugar than the cane-sugar used in 
their household. Urine containing cane-sugar will not reduce Fehling’s or 
Nylander’s solutions before boiling with a dilute mineral acid, but will do so 
after this, and will turn the ray of polarized light to the right. The cane-sugar is 
generally added to the urine in amounts large enough to give it an exceedingly 
high specific gravity, which will immediately turn the physician’s mind in the 
right direction. If the simulator has some knowledge of saccharids, the situa¬ 
tion may be rendered more complicated. He may then contrive to get some 
really diabetic urine and inject it into his bladder ; such a mode of simulation 
can only be detected by keeping the simulator under observation, or by sub¬ 
jecting his blood to Bremer’s test. He is more likely, however, to use the glu- 


* “ Wiener med. Presse,” 1876. 




TREATMENT. 


253 


cose sold for technical purposes. This contains a good deal of dextrin which 
is strongly dextrogyrate, but does not reduce solutions of copper nor bismuth, 
and the fraud is detected by the polarimeter indicating a much higher percent¬ 
age of glucose than do reduction-methods of estimation. 

If simulation by means of phloridzin or phloretin is suspected, the urine 
should be tested with ferric chlorid for the brownish-violet color yielded by 
those substances—it being always borne in mind that a somewhat similar, but 
more reddish, color is caused (1) by diacetic acid in cases of severe diabetes, or 
when starvation is taking place, and (2) in any state of health by antipyrin, 
salicylic acid and its salts, kairin, thallin, chinanisol, and other substances. 
By cutting off the supply of phloridzin or phloretin for fully three days the 
glycosuria due to these poisons can be stopped. 

If one is provided with the proper stains he will probably find in Bremer’s 
method of diagnosticating diabetes (see above) an excellent means of detect¬ 
ing at once any simulation of diabetes in whatever manner it is attempted. 


CHAPTER IX.—TREATMENT. 

Some prophylactic measures may be taken against diabetes ; this 
applies especially to members of families with a neuropathic, a 
gouty, or directly diabetic hereditary predisposition. 

These measures are, in large part, exactly those that are 
rational in cases of nervous disposition. Children that begin life 
thus handicapped ought, still more than others, to be protected 
against fright and other emotions, overwork, and strains of all 
kind, fatiguing and enervating pleasures ; and they should have all 
of the advantages to be derived from fresh air, bodily exercise, baths, 
early hours, and a systematic hygienic life. It is of paramount 
importance, after puberty, to guard such children against an 
abnormal or too early development of sexual activity. It is also an 
exceedingly important and fully rational, though often neglected, 
measure in the choice of a profession to direct such young persons 
to occupations in life that are less likely than others to develop 
neurotic tendencies. In this respect our descendants will certainly 
provide much more carefully than we do or even than we now 
would approve of doing. 

It seems to me that something might also be done in the matter 



2 54 DIABETES MELLITUS AND GLYCOSURIA. 

of diet to diminish an inherited danger of future diabetes, though 
for my part I consider this item of diabetic prophylaxis to be much 
less efficient and important than antineurotic measures. It would 
certainly be most unwise to diminish a child’s supply of bread, 
potatoes, and other more or less necessary articles of chiefly carbo¬ 
hydrate nature below fair daily portions ; but nothing is lost, and 
perhaps something is gained, by a rigorous restriction of sweets 
and sugar in the food of such children. The custom prevalent in 
some countries of including beer and other liquors in the dietary 
of persons even below fifteen years of age might also well be 
avoided. 

It not rarely happens that a diabetic patient asks his physician 
with regard to the advisability of marriage, often, I acknowledge, 
with a firm, though unconscious, resolution in this respect not to 
take advice that is opposed to his own inclinations. If a case 
of true diabetes sets in before the thirty-fifth or fortieth year, life will 
generally be short. Impotence and sterility threaten darkly, and 
pregnancy and maternal duties in woman, like sexual activity in 
man, often favor the development of the dystrophy. The mortality 
among children of diabetic parents, as has been mentioned, is 
enormously high, the constitutional inheritance a great handicap 
in life. It would be unwise for a physician to put all these facts 
distinctly before a patient who thinks of marrying, and who rarely 
is to be dissuaded from doing so, but these arguments must have a 
profound influence on the advice the physician will give. In severe 
cases of diabetes there are left but few of the customary reasons for 
marrying. 

The great dangers for mother and child also ought to be taken 
into consideration in connection with pregnancy in diabetic women, 
and they may, under certain circumstances, justify artificial inter¬ 
ruption of the pregnancy. Such a course in a case of simple glyco¬ 
suria, or even in one of true but mild diabetes in otherwise fairly 
good condition, might justly be considered as malpractice, and the 
mere name of diabetes ought never to be made a safeguard for an 
operation of this kind. I should not hesitate, however, to give my 
vote in favor of interrupting the pregnancy in any case of diabetes 


TREATMENT. 255 

in the severe stage, or in any case in which the prospects of mother 
or child were gloomy. 

There is but little to say outside of general rules with regard to 
the hygiene of diabetic patients. 

The physician and his diabetic patient must never forget the 
small power of the latter to resist deleterious influences of all 
kinds. Diabetics are more likely than others to be affected by 
emotions of a depressing nature and to suffer more in consequence. 
Every physician who has seen much of these patients has learned 
how especially careful one must be not to irritate or in any way to 
frighten them, and he will adopt the rule of according to them, still 
more than to others, the patience and forbearance under all cir¬ 
cumstances—which is not the lightest nor the least important of 
the many high duties of the medical profession. The necessity of 
avoiding all kinds of strains on his nervous system must be earn¬ 
estly impressed upon the patient. He must, as far as possible, 
limit his intellectual activity not only below the level of overwork 
for a normal person but below the level of overwork for his own, 
usually limited, powers. He must be most moderate in sexual 
activity. He must forswear overuse of tobacco and alcohol, 
and it is still more important for him than for others not to fall 
into bad habits with morphin, cocain, somniferous drugs, etc. He 
ought to take as much exercise as he can take without fatigue. 
He must observe regular hours, with a large allowance of time 
for mental and bodily rest. His great sensitiveness to exposure, 
and the especially dangerous consequences of cold make it of par¬ 
amount importance for him to be warmly dressed, and to wear, 
constantly, woolen underclothes. His whole mode of life must be 
thoroughly hygienic. If he lives in a rigorous climate, it is of 
great advantage to him to pass the coldest part of the year in some 
warmer place, observing there the same scrupulously hygienic 
regimen as at home. 

The special duty of taking into earnest consideration the diabetic 
patient’s mental sensitiveness begins at the moment the physician 
discovers the existence of any stage of the glycosuric dystrophy, 
and concerns the statements to be made to the patient on this 
subject. 


256 


DIABETES MELLITUS AND GLYCOSURIA. 


If only a slight glycosuria, but no true diabetes, is found, it is 
in many cases wise to mention nothing about the matter to the 
patient. Individuals of great sensitiveness, especially if not highly 
intelligent, are often greatly affected by learning of the excretion 
of sugar in their urine, however slight and however accentuated by 
the physician its clinical insignificance. If the urine for twenty-four 
hours does not contain more than a trace of glucose (up to 0.05 
per cent.) with an ordinary free diet, and the patient furnishes any 
ground for doubting his courage or judgment, other reasons than 
the existence of glycosuria can always be found for advising avoid¬ 
ance of the most objectionable kinds of food (sweets, dry fruits, rice, 
macaroni, peas, champagne, etc.). 

If the case is one of true diabetes, it is generally necessary to in¬ 
form the patient of this fact. In mild cases the physician then has 
the pleasant task of making the patient acquainted with many actual 
reasons for comfort and hope. In severe cases the physician, who 
alone can determine the nature and prognosis of the special case, 
will understand that, if prudence often is the better part of valor, 
discretion is often the better part of truthfulness. It is quite a 
satisfaction to know that downright lying is generally not necessary. 
The patient usually knows little else of diabetes than that a person 
may live with it for decades in fairly good health, and the physician 
will rather, by repeating this and other general facts, let the patient 
deceive himself than injure and torture him by stating the whole 
implacable truth. 

On the whole, it is of great importance to arrange everything for 
the patient with a view of reminding him as little as possible of his 
own exceptional position. 

For this reason I consider the “ sanatoriums for diabetics,” where the 
patient meets only brothers in misfortune, in many cases to be of doubtful ad¬ 
vantage. The one indication that may arise for a sojourn of some weeks in 
such an institution is the period of absolute or of very rigid diet in the mild 
stage; it depends on circumstances whethergthe dietetic discipline is not even 
then acquired at too high a price. 

The poor diabetic patient certainly derives some advantage from the hos¬ 
pital, where he may for some time enjoy a rational diet at moderate cost. 

One of the diabetic’s most frequent and most common nervous 
symptoms is sleeplessness. This is a trouble that often follows the 


TREATMENT. 


257 


patient throughout his whole life, and it is of the utmost importance 
not to employ remedies that easily lead the patient into bad habits 
and may cause a much greater misfortune even than sleeplessness. 
We therefore, as far as possible, take refuge in simple and harmless 
remedies. We prescribe mental and physical rest during the last 
hours of the day. We recommend the system—already mentioned 
for its merits in other respects—of making the last meal of the day 
a light one, also for its better influence on the night’s rest. A 
moderately warm bath at 35 0 or 36° C. (95 0 or 98.6° F.) before 
going to bed has a good effect in some cases. A hot foot-bath at 
this time and a wet, warm fomentation around the abdomen during 

f 

the night are highly praised by some patients. In other cases I 
have found covering the head warmly at night—with a fur cap, for 
instance—a most efficient remedy for promoting sleep. The vibra¬ 
tions on the head, recommended by Charcot and others, have 
already been mentioned. I found Charcot’s (or Gilles de la Tou- 
rette’s) “ casque vibrant ” too weak, and have seen much better results 
from one of Zander’s machines. One must sometimes try several 
of these simple remedies, and will often find one of them efficient 
when others have failed. 

In the presence of severe exacerbations of insomnia and during 
mental disturbances we are sometimes forced to take refuge in 
narcotic, somniferous drugs. I prefer great economy in this, and I 
rarely give such remedies two nights in succession ; neither do I 
use them for any length of time, if this can possibly be avoided. 
A large dose of the comparatively harmless bromids will diminish 
the necessary dose of other remedies. (I prefer sodium bromid to 
potassium bromid.) Among directly hypnotic remedies, I have, 
after many disappointments, returned to chloral hydrate or chloral- 
amid as the best and least objectionable. With all their draw¬ 
backs, these are decidedly better than the much-praised sulphonal 
and trional, both of which cause drowsiness on the next day, if 
taken in such doses as will cause sleep during the night, and 
both of which cut off the systolic apices on the pulse-curve. 
Among narcotic vegetable derivatives opium and extract of can¬ 
nabis indica rank foremost. Neither morphin nor codein is 
ever to be used for this purpose. One may, for instance, 
give at one dose: sodium bromid, 2 gm. ; chloral hydrate, 


258 DIABETES MELLITUS AND GLYCOSURIA. 

1.20 gm.; extract of cannabis indica, 0.05 gm. ; or some similar 
formula. 

In cases of severe diabetes, with a miserable general state and a 
distinct excretion of /3-oxybutyric acid, our chief task must be as 
long as possible to prevent coma. The patient must with the 
greatest care be protected from injurious influences of all kinds. 
No mental or intellectual exertion, no exposure, no fatigue, no 
long journeys, no deviation from daily customs should be per¬ 
mitted. I add with the deepest conviction that the diet should not 
be made too rigid. The patient may have as much bread, green 
vegetables, and potatoes as he likes ; several teaspoonfuls of levu - 
lose daily will help to keep him alive. It is of paramount im¬ 
portance to promote the excretion of toxins by favoring free diu¬ 
resis. The patient is allowed to drink as much water as he chooses, 
and we especially recommend a generous daily supply of the cus¬ 
tomary alkaline table-waters, charged with free carbonic-acid gas. 
Strong acids ought not to be given ; nor are large amounts of 
alkalies to be recommended for long periods ; if large enough to 
decrease the acidosis considerably, they cause digestive troubles 
and have a weakening effect. It is also most important to keep 
the bowels open by means of massage, aperient drugs,* or by in¬ 
jections. The latter are advantageously performed with large quan¬ 
tities of tepid water and enough potassium permanganate to pro¬ 
duce a faint violet color in the water. 

Whenever there is a danger of coma, great care must be observed 
in the use of narcotic and somniferous remedies. 

When the prodromes appear, or if headache and great lassitude 
raise suspicion of coma, rapid measures may still afford some 
respite. The patient is at once put to bed, receives a glass of 
brandy or of whisky, or a subcutaneous injection of ether, and is 
given enormous amounts of sodium bicarbonate in some water rich 


* I often give : 

Pulveris aloes, ) 

Pulveris rhei, / .aa 4 gm. 

Extract, colocynth. comp.,.3 gm. 

Extract, hyoscyamus,.1.50 gm. M. 

Ft. pil. No. lx. 

SlG.—One, two, or three pills at night. 

The aperient effect of these pills usually follows in the morning. 







TREATMENT. 


259 


in free carbonic acid. A moderate dose of digitalis or strophanthus 
may also be administered. The patient may also take a bath at a 
temperature of 38° or 39 0 C. (100.4° or 101.2 0 F.). 

If matters have progressed still further,—if the respiration is 
dyspneic, the pulse inordinately frequent,—the same steps must be 
taken ; except in exceedingly rare cases neither they nor any other 
means will effect more than a transitory and fallacious improve¬ 
ment. Under such circumstances the alkaline solution may be i?i- 
jected into a vein* but this can not be considered necessary, as it 
presents few advantages over administration of large amounts of 
alkali by the mouth, and' its effects are almost always of short 
duration. The intravenous injection of an alkaline solution requires, 
besides, elaborate contrivances, and is but rarely undertaken in 
private practice. Stadelmann used a concentrated solution of sodium 
bicarbonate and citric acid, and injected 150 cu. cm. three or four 
times a day. Others use solutions of a mixture of sodium chlorid, 
bicarbonate, phosphate, and sulphate. Lepine dissolves 7 grams 
of sodium chlorid and 10 grams of sodium bicarbonate in a liter of 
water ; injects slowly, but within a short while, 2 liters ( ! ! ) of this 
solution at a temperature of 38° C. (100.4° F.) into a vein of the 
arm. 

Whether the intravenous injection be performed or not, a concen¬ 
trated solution of sodium bicarbonate in large doses should always 
be given by the mouth, and a subcutaneous injection of ether or 
caffein citrate may also be given. 

The immediate effect of the alkaline venous injections, or of 
large doses of sodium bicarbonate by the mouth, is sometimes 
apparently favorable, and likely to inspire the inexperienced with 
the hope that the patient will return to his previous state before the 
onset of the symptoms of coma. In the large majority of cases 
this improvement will last only for a few hours or for a couple of 
days, and the physician will do well to prepare those interested for 
the patient’s approaching death, however strongly the comatose 
symptoms have receded for the moment. 

In treating a case of diabetes our first duty—apart from the 


* The subcutaneous injection of large amounts of alkaline solution presents far 
greater inconveniences and dangers than advantages, and ought never be practised. 




26 o 


DIABETES MELLITUS AND GLYCOSURIA. 


almost always hopeless task of removing the cause of the dystrophy 
—is to protect the patient from the inanition that threatens from the 
loss of glucose. Next in importance is the task of providing 
a sufficient number of calories in such food as to cause the least 
possible hyperglycemia and blood toxins, and counteract, as much 
as possible, the development of the diabetes. Dietetic prescriptions 
will thus always constitute an important part of the treatment, though 
they ought not, as is often the case, to make up the whole treatment. 

The facts that ought to form the basis for our views on the dietary 
for a diabetic are as follows : 

1. An individual performing some mechanical work needs from 
thirty-five to forty calories per kilogram of bodily weight in twenty- 
four hours to maintain his nutritive balance. 

2. Proteids yield 3.2, fats 8.4, and carbohydrates 3.8 net calories 
per gram in healthy persons, and usually as much in diabetics— 
minus the loss from glucose in the urine following the ingestion of 
carbohydrates in the mild stage, and present with any diet during 
the severe stage, of the diabetic dystrophy. 

3. Carbohydrates ingested in ordinary amounts cause in all cases 
of diabetes the distinctly, though only slightly, injurious hypergly¬ 
cemia, which finds its expression in the, per se, almost indifferent 
glycosuria. 

4. All diabetic patients, however, utilize some portion of ingested 
carbohydrates, and the calories thus gained contribute better than 
calories derived from fat to the protection of the organism’s own 
proteids. Levulose is better utilized than any other yet known 
and fully acknowledged carbohydrate. 

5. Restriction of carbohydrates in the food causes a decrease or 
a cessation of hyperglycemia and glycosuria, and, apart from other 
advantages, counteracts the development of the glycosuric dys¬ 
trophy. 

6. Fat, ingested in any quantity, does not cause hyperglycemia 
or glycosuria in any stage of diabetes. 

7. Fat, however, in spite of its high caloric value, can not be 
ingested in any quantity that even remotely covers the expenses of 
the organism. 

8. Still, fat can be ingested in much larger quantity with than 
without the ingestion of carbohydrates. 


TREATMENT. 


26l 


9. In cases of severe diabetes toxins arise in the blood that are 
far more injurious that the hyperglycemia. 

10. These toxins are increased by exclusion or too rigid a 
restriction of carbohydrates from the food. 

11. Normal human food—apart from water and salts—consists 
of proteid, fat, and carbohydrate, and permanent exclusion of car¬ 
bohydrate from the diet can not be effected, because it prevents the 
supply of a sufficient quantity of calories and causes severe dis¬ 
turbances of the digestive functions. 

12. Among articles of food rich in carbohydrate bread is most 
difficult to exclude. 

A rational diet for a diabetic must be founded on all these facts ; 
if too much importance be attached to dangers or to advantages 
of any special kind, the treatment necessarily will be defective. 

An absolute diet—by which I mean a diet of meat and fat with 
the strictest possible exclusion of carbohydrates—can never be 
followed for periods of more than weeks, or, at the longest, of 
months. I consider the correctness of this opinion to be so univer¬ 
sally acknowledged at the present time that it is unnecessary to 
spend more words on it. 

It remains, then, to decide in which cases of diabetes it may be 
advantageous periodically to exclude carbohydrates* from the food. 

This may advantageously be done in most cases within the mild 
diabetic stage. Even with robust individuals in that stage, how¬ 
ever, I do not find it rational to prescribe, nor could I prevail upon 
the patient to submit to, longer periods of absolute diet than a 
month. 

The advantages of the absolute diet in mild cases consist in the 
cessation of the hyperglycemia and its effects, the cessation in itself 
counteracting the progressive tendency of the diabetes and often 
increasing the power of assimilating carbohydrates. 

The disadvantages of the absolute diet, even in mild cases, are, 


* Unfortunately for diabetics, bread is the kind of food that most people find it most 
difficult to spare. If any one should for a time live on only two of the three kinds of 
food,—meat, butter, and bread,—he would want first of all the bread and resign the butter. 
It is also known that large, fairly civilized populations chiefly (and up to more than go 
per cent, of the whole solid food) live on rice, but meat and fat nowhere constitute so 
large a part of the food, except among the few and low-ranking tribes in the Arctics. 



262 


DIABETES MELLITUS AND GLYCOSURIA. 


unfortunately, very great. The patients with this diet often suffer 
from constipation, which is likely to give way only to diarrhea. They 
lose their appetite and are not able to ingest much fat or enough 
of any permitted food to maintain their nutritive balance ; they almost 
invariably lose flesh. The neurasthenic symptoms, rarely absent 
in cases of diabetes, are especially prone to be aggravated by the 
inanition. The mere absence of normal pleasure and satisfaction at 
meals also has, in many cases, an unfortunate effect on the patient’s 
mental state. 

It will generally be found that the patient will bear better the 
absolute diet, and derive greater advantages from it, the fatter and 
the less nervous he is. The state of the digestive organs and their 
power to support the absolute diet is also a most important and 
a most varying factor. It must also be remembered that there are 
in apparently quite similar cases great individual differences in the 
capability of supporting and in the general effects of the absolute 
diet. I have sometimes, even in mild cases of diabetes, found it 
wiser, after a signal failure, never to prescribe the absolute diet, 
from which some patients suffer exceedingly in their general state 
and well-being. 

In the severe stage the advantages to be derived from the abso¬ 
lute diet are always much diminished. We can no longer free the 
patient from the hyperglycemia and its effects, and we can no 
longer materially increase his power of assimilating carbohydrates. 
The disadvantages arising from a rigid exclusion of carbohydrates 
are much greater than in the mild stage, and the increase of acetone, 
diacetic acid, and / 5 -oxybutyric acid, inseparable from such a diet, 
also directly increases the danger of coma, which, besides, becomes 
greater by reason of the inanition itself, scarcely to be avoided 
upon exclusion of carbohydrates. 

The rational application of these facts forbids the exclusion of car¬ 
bohydrates in the distinctly severe stage of diabetes. 

In determining the daily allowance of carbohydrates for a patient 
in the severe stage I must, however, distinguish between two classes 
of patients. 

The first class consists of cases presenting diacetic acid but 
no / 3 -oxybutyric acid in the urine. There is in these cases no 
danger of coma; but the patients generally have lost in bodily 


TREATMENT. 


263 


weight, and are in a poor state of general health. An exclusion of 
carbohydrate seems to me, even in these cases, to do more harm 
than good, by decreasing their bodily weight and by exerting a bad 
influence on the general somatic and mental state. I customarily 
allow such patients from eighty to one hundred grams of carbohy¬ 
drate in twenty-four hours ; usually, at least half of this portion is 
taken in bread and the rest in vegetables of different kinds (see 
below). 

The second class of severe cases consists of those in whose urine, 
in addition to diacetic acid, also / 5 -oxybutyric acid is present: i. e. } 
cases in constant danger,-more or less pronounced, of coma. 
Whenever I encounter a diabetic patient in the distinctly severe 
stage, I allow him a moderate daily amount of carbohydrates 
(eighty grams) until I have acquired definite information on this 
point. If after the removal of all sugar from the urine by fermen¬ 
tation, and of combined (levogyrate) glycuronic acids by precipitation 
with lead acetate and ammonia, I still find distinct levogyration, 
denoting the presence of , 3 -oxybutyric acid and at the same time 
an advanced “ acidosis ” (in the blood), I am averse to any great re¬ 
striction of carbohydrates. However absolutely I condemn an ex¬ 
clusion, if ever so short, of carbohydrates in these cases, I am 
willing to admit that the rational daily amount of carbohydrate is 
a matter open to discussion. Considerable experience, however, 
both of the effect of my own dietetic system and of that of other 
physicians, has forced me to the conclusion that I promote best the 
interests of such patients by allowing them a generous, if not an 
unlimited, amount of bread * and potatoes. I exclude from their 
dietary only such articles as contain much carbohydrate and at the 
same time can easily be spared (rice, macaroni, peas, dried or sweet 
fruits, sugar and sweets, champagne, beer, sweet wines and liquors, 
etc.). In these cases, if circumstances permit, I also use levulose, 
recommending it strongly as a substitute for cane-sugar. It in¬ 
variably increases the glycosuria, but as invariably diminishes the 
autophagy and loss of weight, and I believe that it has in many of 
my own cases postponed the final issue. 


* In cases with advanced acidosis I allow at least one hundred grams of ordinary 
white bread a day. 




264 DIABETES MELLITUS AND GLYCOSURIA. 

If a patient in the advanced severe stage is, after some allowance 
of carbohydrate in his food, put on an exclusive animal regime, or 
only allowed a small daily amount of carbohydrate, he frequently 
is attacked and killed by coma within a few days. 

“ But,” some one will say, “ the absolute diet has also a diagnostic 
purpose ; and how shall I ascertain the state of the patient’s dystro¬ 
phy without putting him on an exclusive animal diet, with a 
minimum of carbohydrate ? ” I have already answered this objection. 
If a diabetic patient on a mixed diet passes urine that does not 
yield a distinct Gerhardt’s reaction (a wine-red color on addition of 
a solution of ferric chlorid), I may, without danger of coma, with¬ 
draw the carbohydrate. If the urine presents a distinct Gerhardt’s 
reaction, the case is a severe one, and it would be a grave error to 
put him on an absolute diet. 

In my opinion we must adopt the rule in all cases of diabetes, 
mild or severe, never, as a permanent dietetic rule, to put any 
maximum limit, any restriction, on the supply of meat or fat. There 
are cases on the borderland between mild and severe diabetes that 
with exclusion of carbohydrates and some restriction of meat pre¬ 
sent no glycosuria, and that with exclusion of carbohydrates, but 
with a larger supply of meat, excrete small quantities of glucose. 
A restriction of meat also in many other cases diminishes the 
glycosuria. The slight corresponding hyperglycemia, however, is 
an insignificant matter as compared with too much prescribing and, 
above all, with underfeeding. When one of Germany’s greatest 
clinicians and best authorities on diabetes (Naunyn) recommends a 
maximum limit in the supply of meat,* even with an exclusion of 
carbohydrates,—which he also prescribes in cases in the severe stage, 
—with all my admiration for him personally and for his work, I can 
not follow him here. How could a patient who has to live exclu¬ 
sively on meat and fat avoid underfeeding if he is not permitted, 
even with regard to this poor food, to satisfy his appetite, which on 
this point affords more trustworthy indications than are sometimes 
given by learned and otherwise clever physicians ? 

The danger from underfeeding with exclusion or strong restric- 


*So far as I know, Rollo was the first to urge a restriction even of proteids in cases 
of diabetes. I have no doubt that this dietetic principle is at present on its last legs. 



TREATMENT. 


265 

tion of carbohydrates is always imminent, and rather than restrict 
proteids and fat, we ought as much as possible to insure the patient 
against receiving too small amounts of both for the maintenance of 
his nutritive equilibrium. Even when we do our best, we shall find 
that a marked restriction of carbohydrates often necessarily results 
in some degree of starvation. 

Let us consider the dietetic needs of a man of seventy-five kilo¬ 
grams of bodily weight who receives forty calories per kilogram in 
twenty-four hours, and how to meet those needs with different pro¬ 
portions of the three great classes of food. I shall, as far as possi¬ 
ble, confine myself to round figures in making the whole amount of 
the daily supply reach about 3000 calories : 


Case. 

Proteid. 
Net Value, 
3.2 Cal. 

Fat. 

Net Value, 
8.4 Cal. 

Carbohy¬ 
drate. 
Net Value, 
3.8 Cal. 

Sums of Calories. 

No. 1 

135 g m - 

80 gm. 

500 gm. 

= 432 + 672 + 1900 = 3004 

“ 2 

420 “ 

200 “ 

0 “ 

= 1344 + 1680 -f 0 == 3024 

“ 3 

120 “ 

285 “ 

60 “ 

= 384 -f 2394 + 228 = 3006 

“ 4 

0 

0 

65 “ 

60 “ 

= 2240 -f- 546 -f- 228 = 3014 

“ 5 

185 “ 

260 “ 

60 “ 

== 592 + 2184 -f- 228 = 3004 

“ 6 

225 “ 

245 “ 

60 “ 

= 720 4- 2058 -(- 228 = 3006 

“ 7 

250 “ 

235 “ 

60 “ 

— 800 4- 1974 -f- 228 = 3002 

“ 8 

345 “ 

200 “ 

60 “ 

= 1104 4- 1680 4- 228 == 3012 

“ 9 

300 “ 

200 “ 

loo “ 

= 960 4- 1680 4- 380 = 3020 

“ 10 

190 “ 

24O “ 

100 “ 

= 608 -j- 2016 4- 380 = 3004 


The first line in the table shows an arrangement that gives 
fifteen grams more of proteid and twenty-five grams more of fat 
with the same amount of carbohydrate than Voit’s classic table. 
I have made the additions necessary to reach the 3000 calories to 
the proteids and to fat, because the patient, of his own choice, fol¬ 
lowing only the dictates of taste, is much more likely to do this 
than to increase the amount of carbohydrate above 500 grams. 
Among Anglo-Saxon and Teutonic nations the free choice of pro¬ 
portions for 3000 calories would often increase the proteids to at 
least 150 grams, and the fat to an equally large or even larger 

amount. 

18 




























































266 


DIABETES MELLITUS AND GLYCOSURIA. 


The second line in the table shows at a glance how very difficult 
it is to obtain the 3000 calories without carbohydrate. If we put the 
fat at 200 grams,—which for many individuals represent the maxi¬ 
mum possible of ingestion, and which are contained in about 240 
grams of butter,—we must take 420 grams of proteid or nearly 1250 
grams of cooked meat (free from fat). If we trust to the ability of 
the patient to take daily ten eggs, each of which shall contain fifty 
grams of food, we may decrease the meat by about 200 grams, and 
the butter by about fifty-four grams ; but how many individuals are 
able to eat fully a kilogram of meat, nearly ^ of a kilogram of butter, 
and ten eggs a day, even if the most expert chefs put their heads 
together to make the whole as palatable as possible ? 

The third and the fourth lines in the table only show that, 
even if I allow sixty grams, or the minimum of carbohydrate that is 
necessary in the long run, by increasing only the proteids or only 
the fat, I obtain perfectly impossible quantities of the one or the 
other. 

The fifth, sixth, seventh, and eighth lines represent the possi¬ 
bilities of ingesting enough of proteids and fat in addition to the 
necessary minimum of carbohydrate ; but we find that however the 
proportions of proteids and fat are arranged, the patient is likely to 
have before him a difficult task. 

The ninth and tenth lines show how the patient’s task is facili¬ 
tated by allowing him a somewhat larger amount of carbohy¬ 
drate. There are a great many persons of 75 kilograms of bodily 
weight who are able to keep themselves in a fair state of health by 
ingesting in the twenty-four hours 190 grams of proteids, 240 
grams of fat, and 100 grams of carbohydrate, or about 2.5 grams 
of proteid and 3.2 grams of fat per kilogram bodily weight. The 
quantity of fat is rather large ; in many cases it will be necessary to 
diminish this and to increase the amount of proteids to something 
more like the quantities given in the ninth column. But the more 
fat a diabetic can ingest, the better off he is, and a patient of 75 
kilograms ought, if possible, not ingest less than 200 grams of it. 
The ninth and tenth lines show proportions that, especially in 
mild cases, will often be found in the long run to be the most 
advantageous. In very severe cases 100 grams of carbohydrate are, 
for a person of this weight, never too much, but often too little. 


TREATMENT. 


267 


In this table I have not taken into consideration the loss of calo¬ 
ries represented by the glucose in the urine. On the other hand, I 
have not taken into consideration the calories that may be gained 
by the use of a moderate amount of alcohol. If we put the 
caloric value of glucose at 3.7 per gram, we find that a patient that 
passes 50 grams of glucose in the twenty-four hours—a large 
amount in the mild stage with a daily supply of 100 grams of car¬ 
bohydrate—loses 185 calories of what he has ingested and digested. 
This loss is not larger than the allowance of alcohol—equivalent to 
7 calories per gram—that can be accorded to a person of 75 kilo¬ 
grams. 


Rollo was the first, in the beginning of this century, to recommend an exclu¬ 
sive diet of meat and fat in cases of diabetes. He committed the error, after- 
terward repeated by others, of prescribing a restriction even of meat. In 
those days the laws of nutrition and the organism’s imperative demands for 
a certain number of calories were not known, and importance was attached 
almost exclusively to a removal of the glycosuria. Rollo, however, in his 
practice did not carry out his theories with regard to an exclusively animal diet, 
which, according to his prescription, was adopted throughout Great Britain and 
its colonies, and soon spread to France and Germany. Wherever this system 
was introduced it proved unsatisfactory, from the consequent disturbances of 
digestion, its manifest insufficiency, and from the patient’s invariable aversion. 
Opinions on this subject have since been much divided, and are so to some 
extent at the present time. Bouchardat (from 1842) contributed largely to the 
establishment of a better system with a mixed diet of ingestable quantities of 
meat and fat, and a restricted supply of starch, chiefly taken in the form of green 
vegetables and bread ; he also allowed moderate quantities of alcohol. Mean¬ 
while, Prout introduced gluten-bread and inaugurated the long series of breads 
made especially for diabetics. 

The late distinguished Neapolitan physician, Cantani, was one of the most 
energetic advocates in our time of an absolute (animal) diet for cases of dia¬ 
betes. He allowed only meat and fat, and as representatives of the latter he 
recommended olive oil and cod-liver oil. Butter was forbidden because it con¬ 
tains a trace of milk-sugar. Cantani later became somewhat more reasonable, 
and allowed butter and “frutti di mare" a dish composed of different small 
salt-water animals, some of which contain a considerable percentage of gly¬ 
cogen. It was his plan to enforce this diet for at least three months, and then 
gradually to make concessions toward a more mixed food. One gains quite a 
curious impression from reading Cantani’s opinions with regard to the possi¬ 
bilities and the effects of the severe regime he prescribed. I suspect that some 
of his patients have, without his knowledge, smuggled not inconsiderable 
quantities of macaroni into their food. Cantani spent his life in Naples, with 
its heavenly nature and vile population, by whom a true word, to quote Swin¬ 
burne, in “ Peter Simple,” seems to be spoken only by mistake. 


268 


DIABETES MELLITUS AND GLYCOSURIA. 


An absolute diet in the severe stage of diabetes is now insisted upon strictly 
by Naunyn and his school. Even his justly honored name is not sufficient to 
sustain this position. The cases published by him and his disciples demon¬ 
strate what this regime is capable of effecting in the severe stage; the patients 
immediately after its inception being often delivered from their sufferings by 
death in coma. 

It is a pleasure to know that the absolute diet has certainly never been 
observed, except for a very short time, by any one not kept under lock and 
key. A considerable experience with cases of diabetes in representatives of 
the best nations and of the best (z. <?., most educated, most intelligent, and 
therefore most reliable and obedient) classes, has taught me that the physician, 
even if he knows how to acquire the confidence of his patients, can only rarely 
enforce abstinence from carbohydrates (bread) for as long time as a month, and 
that any one by unreasonable demands in this respect only incurs the danger 
of not being obeyed even in feasible matters. 

Experience no less than late advances in physiology and experimental 
pathology should prevent us from permitting our fears of hyperglycemia with 
its glycosuria to overshadow other and greater dangers. 

There died in Sweden some years ago a man whose case is an illustration 
of the comparatively insignificant danger of hyperglycemia. The patient was 
Professor Forsell, well known from his paper on his own case, published in 
1883. Forsell was no physician, and his paper bears the stamp of the layman. 
Some of his conclusions are entirely false. The facts with regard to his diet, 
his polyuria, and his glycosuria, however, are certainly in the main correct, 
and correspond with the data of his physician, who died a few years ago. 
Forsell’s diabetes began quite suddenly in 1866; the same year the percentage 
of sugar reached 7.4, the polyuria 6.5 liters, the specific gravity 1.040, the daily 
loss of glucose often 425 grams, and on one occasion 850 grams. Professor 
Forsell never was my patient, and I am not familiar with the details of his 
case ; but although its course proves it to have remained at least for a consider¬ 
able length of time in the mild stage, there is no doubt that it was, in 1866, 
already quite an intense diabetes. His physician at first put him on a strict 
diet; unfortunately, there is no record of its effect on the glycosuria. Forsell, 
however, soon found that the strict diet, besides being exceedingly unpleasant, 
always made him feel ill and weak. Having ascertained the evil consequences 
of this system, he adopted the opposite extreme, consuming a considerable 
amount of bread and of vegetables, and every day drinking from 6 to 8 pints 
of Bavarian beer. “ By avoiding diet, watering-places, and medicine, I have 
kept in very fair health since 1873,” Forsell writes in 1883. When Forsell died, 
he had suffered from most pronounced diabetes for about twenty years. Such 
a prolongation of life in cases of this kind is extremely rare—much rarer than 
it is for a gouty person with mild diabetes to live for forty years. Is there 
any reason for believing that Forsell’s life would have been longer or happier 
if he had lived on meat and fat, without carbohydrate or with a scanty supply ? 

I am particularly anxious not to be accused of approving of Forsell’s 
regime. I am perfectly certain that he might, with advantage, have made some 
restrictions in carbohydrate—and no one will approve of his enormous consump- 


TREATMENT. 


269 


tion of Bavarian beer. The mere fact, however, that a diabetic of this kind can 
live in fairly good health and do fairly good work for more than twenty years 
is worthy of consideration, and may afford a foundation for conclusions that, 
however prudently formulated, are of great practical portent. Professor For- 
sell’s was far from being a good regime, but I feel convinced that if I had to 
choose for my patients—as a rule, for years—between his regime and an exclu¬ 
sion or a severe restriction of carbohydrates, I should act wisely in choosing 
the former. 

In the mild stage we always have to put a maximum limit upon 
the daily amounts of carbohydrate. Except in dealing with a cer¬ 
tain kind of hypochondriacal patients, we need not trouble our¬ 
selves with regard to a minimum limit. In the enormous majority of 
cases we may feel certain that if the patient does not consume more 
carbohydrate than we prescribe, he will hardly ever consume less. 

In a large number of cases the rational daily allowance of carbo¬ 
hydrate is represented by the maximum that the patient can take 
without the development of glycosuria. We should never restrict 
the patient’s allowance of carbohydrate below the amount that 
leaves him free from sugar in his urine, and thus free from any dis¬ 
tinct hyperglycemia. Whenever a patient can take the necessary 
amount of carbohydrates for the maintenance of good digestive 
action and nutritive equilibrium, without the development of glyco¬ 
suria, he is permitted to take that amount. According to my 
experience, the minimum amount sufficient in the long run for a 
full-grown person is hardly ever less than 60 grams of carbohy¬ 
drate, and is usually somewhat more. On the other hand, it is 
rarely necessary to give a diabetic patient in the mild stage more 
than 100 grams of carbohydrate; neither is he capable of taking 
more for any great length of time without the development of 
glycosuria. The rational daily allowance of carbohydrate for pro¬ 
tracted periods for a patient in the mild stage thus varies usually 
from 60 to 100 grams. For reasons mentioned in the preceding 
chapter, it is well to determine the amount in each case by giving 
the patient the larger quantity (100 grams) and diminishing it until 
the glycosuria ceases,* or until the necessary minimum (of about 60 
grams) for constant use has been determined. 

* We consider the glycosuria practically to have ceased when Nylander’s and Feh- 
ling’s solutions react only faintly with a sample of the urine collected during twenty- 
four hours. 




270 


DIABETES MELLITUS AND GLYCOSURIA. 


If the patient (in the mild stage) continues to exhibit glycosuria 
when his daily allowance of carbohydrate is restricted to the mini¬ 
mum necessary for maintaining good digestive activity and nutritive 
equilibrium, it is preferable to risk the moderate disadvantages of 
the slight corresponding hyperglycemia rather than the more serious 
dangers of digestive disturbances and inanition. The rational daily 
allowance of carbohydrate varies not only among individuals, but 
also from time to time in the same individual. Sometimes loss of 
appetite or of flesh, exacerbation of neurasthenic symptoms, mental 
inability to submit to some restrictions, force us to make some con¬ 
cessions. In cases complicated by gout, the hope, always faint, of 
bringing about recovery from the diabetes by removing the hyper¬ 
glycemia is lost. The chances that the diabetes will remain mild 
are almost certain, and we are not inclined to be severe, especially 
as we have no wish to increase too greatly the proteids, and 
thus to put a strain on the kidneys, and as we need bread to 
facilitate the ingestion of the necessary amount of fat. The further 
advanced in age the patient, the less danger there is of his ever 
reaching the severe stage of diabetes, and we can afford to be 
more liberal; in senile cases we never urge severe restrictive 
measures. 

If, on the other hand, there is reason to believe a case of diabetes 
to be of quite recent origin, we should always estimate at its full 
value the increased chance, however small, of perfect recovery by 
removal of the hyperglycemia, and for a long while we restrict the 
carbohydrate as much as possible. During healing processes of all 
kinds, or before an operation, it is also desirable to remove as much 
as possible the hyperglycemia. Finally, a sudden decline in a 
diabetic patient’s power of assimilating carbohydrate makes a rigid 
restriction necessary. 

In those cases in the mild stage in which the patient’s power of 
assimilating carbohydrate is too low to permit of the usual diminu¬ 
tion of his daily allowance below his limit of assimilation and of 
the removal of his hyperglycemia there remain several ways of 
mitigating the hyperglycemia and its effects. 

For this purpose the patient may be advised to take his whole 
daily allowance of carbohydrate during his first one or two meals 
of the day ; the physician should not forget to insist that he shall 


TREATMENT. 


271 


at the same time take as much butter as possible with his bread. 
By entirely excluding or markedly restricting the carbohydrates of 
the last meal the hyperglycemia also is excluded or restricted 
during the larger part of the twenty-four hours. The last meal, 
thus consisting exclusively of animal food, will then necessarily 
tend to be a light one. The German system, with an early dinner, 
is better for this purpose than the custom prevailing in France, 
England, and the United States, of taking the heaviest meal in the 
evening. 

There is still another way of mitigating the hyperglycemia and 
its effects in those cases in the mild stage in which even the 
minimum daily allowance of bread and vegetables necessary for the 
maintenance of digestive activity and nutritive equilibrium cause 
glycosuria and hyperglycemia. For this purpose periods of exclu¬ 
sion or of such severe restriction of carbohydrates are prescribed 
that the glycosuria, beyond faint traces in the mixed urine, dis¬ 
appears. Such periods may be prescribed several times a year ; 
they ought to last for at least two weeks, but can scarcely ever be 
enforced for more than four weeks. If loss of weight, neurasthenic 
symptoms, and digestive disturbances become too marked, we have 
to shorten these periods, which rarely pass entirely without some 
of the troubles mentioned. If one prescribes periods of this kind 
of as long a duration as four weeks, he may with advantage select 
the summer for one and the winter for another. In the spring and 
in the autumn the tendency to mental depression, common among 
diabetics, is more marked, at least in northern climates. 

The absolute or severe diet includes all animal food except milk 
(and its derivative, cheese), with its nearly five per cent, of lactose, 
and liver, with its variable, but usually small, amount of glycogen. 
It thus allows all otherwise wholesome parts of mammals , birds , 
amphibia (turtles, frogs, etc.), fishes, lobsters , crabs , crawfish , oysters , 
etc. It would be unwise and pedantic to exclude from this 
frugal dietary eggs and butter , on account of the insignificant pro¬ 
portion of carbohydrates they contain. Eggs are easily taken, 
easily digested, and, apart from idiosyncrasies, constitute an impor¬ 
tant item in the severe diet. The butter with its eighty-four per cent, 
of pure fat usually represents among Teutons and Anglo-Saxons 
the greater part of the fat in the food, and more than is taken in 


2 72 


DIABETES MELLITUS AND GLYCOSURIA. 


bacon, meat of any kind, lard, olive-oil, milk, cheese, eggs, etc., 
put together. The butter tastes better, is more easily ingested and 
digested than most other fats, and has, besides, the great merit of 
not reminding the diabetic, by any rarity of appearance, of his con¬ 
dition. It is therefore somewhat incomprehensible why so many 
diabetics, except for special indications, are tortured with that un¬ 
palatable fat, cod-liver oil. Neither can I understand the superiority 
of either olive-oil or “ lipanin ” to butter, which certainly contrib¬ 
utes better than anything else to the possibility of ingesting the 
desirable amount of fat. Unfortunately, few persons are able to take 
large amounts even of butter without bread. 

It is a most important rule to give the patient with the severe diet 
the advantage of as great a variety of food as possible, and to 
include different kinds of meat, birds, fish, and eggs in his dietary. 
When his digestive power is weak, he often derives considerable 
benefit from the modern condensed forms of proteid food. I have 
especially often seen good effects from the use of “ somatose, ” 
which is rich in albumoses. 

But whatever is done, the patient will have a trying time during 
periods when an exclusively animal diet is demanded and it is often 
possible, even during periods of rigid restriction, considerably to 
mitigate his dietetic difficulties by introducing into his food small 
quantities of those vegetables that contain comparatively slight 
amounts of carbohydrates. The German “ sauerkraut ” the French 
“ choucroute”. when well fermented, does not contain more than a 
few tenths of a per cent, of carbohydrate. String-beans , picked 
quite young and before the development of their seeds,* contain 
much inosite, but only traces of carbohydrate. Lettuce , cucumbers , 
and in many cases the leaves of spinach may also often be taken in 
small quantities by patients in an advanced mild stage, without 
causing the appearance of more than faint traces of glucose in their 
urine. The mitigation that such an addition to the dietary affords 
during periods of severe restriction is often underrated by the 
physician, but never by the patient. 


* When the seeds are developed, string-beans contain several per cent, of starch and 
sugar, and they no longer constitute an appropriate article of food during periods of rigid 
dietetic restriction. 



TREATMENT. 


273 


During periods of anything like rigid restriction of carbohy¬ 
drates, the diabetic patient has to choose between two substitutes 
for bread. The one is the genuine , tasteless, expensive, and almost 
worthless ‘‘gluten-bread,” of which I have entirely abandoned the 
use. The other substitute for bread is the “bread ” made accord¬ 
ing to Pavy’s and Seegen’s prescriptions, of eggs, butter, and 
almonds deprived of their sugar. The almond bread which, as 
bought in shops, usually contains starch, ought to be baked at 
home, according to the original prescription,* and can even then, 
during periods of severe restriction, be allowed only in small 
amounts. 

The most important question of bread, which must be treated at 
some length, leads me to the subject of the more liberal diabetic diet , 
in which at least half, often more, of the allowance of carbohydrate 
is given in the form of bread. All proper bread certainly contains a 
large percentage of starch, but the human digestive apparatus is too 
accustomed to this kind of food to be able to get along entirely with¬ 
out it. The bread, besides its other nutritive value, also facilitates the 
ingestion of fat, which, from its high caloric value and its properties 
of not increasing either the hyperglycemia or the work of the kid¬ 
neys is so advantageous to diabetics. In discussing the question 
of bread with a diabetic patient the physician should never fail to 
point out its merit as an excellent vehicle for fat, and impose upon 
him the necessity of always taking butter, or butter and cheese, 
with his bread. 

The impossibility of living without bread and the fear of its 
starch for diabetics have led to many attempts to produce for 
these patients something that might possess the advantages of 
ordinary bread without supplying the much-dreaded starch. I be- 

1 

lieve this problem to be as impossible of solution as the squaring 
of the circle or as the problem of perpetual motion. It is the 


* The powder of one-quarter pound dried and finely pulverized almonds is put in a 
linen bag and cooked a quarter of an hour in water with some drops of vinegar, then 
well kneaded with three and a half ounces of butter and two whole eggs. Then the 
yolks of three other eggs and some salt are added to the mass. The whites of the three 
eggs are well beaten and also added, whereupon the whole is put in a buttered form and 
baked. When prepared in this legitimate way, without meal or rice, the bread unfortu¬ 
nately often lacks the proper consistency. 



274 


DIABETES MELLITUS AND GLYCOSURIA. 


starch in the bread that chiefly gives it its good taste and other 
dietetic merits, and that diabetics, as well as others, need. Every 
one of the many “breads for diabetics ” suffers from either of two 
faults : it contains much starch or it does not taste like real bread, 
and is a substitute for it in almost nothing but name. Further, dis¬ 
honest speculation has furnished the market with a great number 
of preparations whose real qualities are concealed beneath false or 
ambiguous assertions. At this moment there is before me a cir¬ 
cular from a baker, accompanied by a sample of his aleuronat-bread , 
—the former couched in such terms as to make the reader believe 
that the ready-made bread contains only the comparatively few per 
cent, of starch of the original aleuronat, while in reality it contains, 
at the very least, four times that amount. Patients easily persuade 
themselves that they may consume any amount of any bread that 
is said to be especially prepared for diabetics. This is the case 
even with the ordinary Graham bread , which contains about forty 
per cent., by weight, of pure starch, or nearly eighty per cent, of 
what is contained in the same quantity of white bread. The prep¬ 
arations with a small amount of starch or with none at all are 
tasteless, indigestible, and expensive. Upon the whole I am of the 
opinion that the “breads for diabetics” have profited the bakers, 
but injured the diabetics. 

I would advise physicians to allow their diabetic patients, except 
during periods of rigid restriction of diet, daily a fixed amount of 
the kind of ordinary bread that they prefer. It is only important 
to limit the daily allowance either by weighing it every morning or 
by buying it in some customary form containing practically a fixed 
and definite quantity. If the measurement of the quantity is left to 
the patient’s eye, it will not be long before the urine will show that 
he has taken far too much of it. 

Graham bread tastes well, but contains about forty per cent, of starch. 
Bran-bread , a la Prout or Camplin, tastes badly, otherwise it contains too 
little bran and too much starch. Bread may be baked from inulin, a substance 
found in the roots of certain Compositse (inula, taraxacum, dahlia, etc.). 
This bread, producing levulose and not glucose, causes much less glycosuria 
than starch, but it has a poor taste. Soya-bread , from the Japanese Soya his- 
pida, demands twenty per cent, of starch to render its taste at all pleasant. 
Dika-bread, made from owala-seeds or the fruits of the African Pe?itaclethra 
macrophylla (30.5 per cent, proteids and 45.18 per cent, of fat), is still unknown 


TREATMENT. 


275 

to me, but does not seem to have made much progress as a food for diabetics. 
The meat-bread of Baron Liihdorf contains much starch. In describing its taste 
as pleasant, the Baron does so without frenzied protests, only by virtue of the 
proverb “ de gustibus non est disputandum.” Genuine gluten-bread is per¬ 
fectly tasteless; what is called gluten-bread generally contains three-fourths 
as much starch as an equal weight of ordinary white bread. As to “ florador,” 
“ semolina,” and other preparations of like kind, they differ from ordinary 
bread chiefly in their price. 

So far as I know, there are, among the enormous number of “ breads for 
diabetics” at present, only two of those mentioned that really deserve the 
attention of physicians—viz., Pavy-Seegen’s almond bread , and Hundhausen’s 
aleuronat bread. I sometimes, as already mentioned, during periods of rigid 
diet make use of almond-bread, which, prepared in the proper manner, contains 
only insignificant quantities of carbohydrates. On boiling with the addition of 
a few drops of acetic acid to the water, the greater part of the nine per cent, of 
sugar and dextrin is removed, and twenty-four per cent, of emulsin and fifty- 
four per cent, of fat are left. For the market, however, the bread is often baked 
with the addition of some flour to give better consistency. It is not easy to 
digest; it is expensive ; and it has a dry, unsatisfactory taste; but it is capable 
of serving the purpose already mentioned. Aleuronat consists chiefly of vege¬ 
table proteids. Hundhausen’s preparation contains about eighty per cent, of 
that substance, 8.7 per cent, of water, and eight per cent, of carbohydrate. By 
mixing it with wheat-flour one may produce a bread that contains less starch 
than ordinary bread, and that tastes the better the more wheat-flour it contains. 
If Hundhausen’s aleuronat flour is mixed with an equal weight of wheat-flour 
(the minimum amount of the latter necessary to make a fairly pleasant tasting 
bread), the whole mixed dry meal contains 45.1 per cent, of proteids, 41.35 per 
cent, of carbohydrate, and 11.05 per cent, of water. The bread will thus con¬ 
tain nearly as much carbohydrate as it does proteid; it tastes much less well 
and is much more expensive than ordinary bread. Its merit is that it contains 
less carbohydrate than ordinary bread—not that it contains vegetable proteid, 
which tastes less well, and is much less digestible than animal proteid, as it 
leaves as much as twenty-five per cent, undigested in the feces. Ebstein 
recommends the unmixed aleuronat flour for sauces and for the grilling of 
meat; about twice as much of it is taken for these purposes as of wheat-flour. 

It is not to be denied that a diabetic patient may derive some advantage 
from using bread made of as much of aleuronat and as little of wheat-flour as 
will do for him in the long run, thus obtaining a larger amount of bread, as 
compared to its quantity of starch, as a vehicle for cheese and butter. Even 
aleuronat bread, in some respects the best of all “ breads for diabetics,” has the 
one merit common to them all— i. e., it is not absolutely necessary. If the 
physician wishes to prescribe this special bread, he had better have his patient 
buy Hundhausen’s original aleuronat, and bake the bread at home. This is the 
only easy way of ascertaining its percentage of carbohydrate. 

Diabetics, like other persons, know better what they want in the 
way of food than with regard to anything else. They almost all 


276 DIABETES MELLITUS AND GLYCOSURIA. 

want not only bread, but also potatoes. Now, there are many things 
that contain more starch than potatoes ; but the cooked potatoes 
containing at the least fifteen per cent, of starch and little besides 
but water, we ought to persuade our diabetic patients to do without 
it, as our ancestors had to do a couple of hundred years ago. When 
the power of assimilation is active, or when a certain amount of 
hyperglycemia may be tolerated, we may allow a small quantity of 
potatoes, always insisting upon the amount being weighed, and upon 
their being used as a vehicle for butter, in which capacity they fulfil 
a most useful purpose. 

Attempts to find a substitute for potatoes have not been much 
more successful than those to find a substitute for bread. The 
tubers of Helianthus tuberosns L., the Jerusalem artichokes, by 
reason of the fact that they contain, when fully developed,* very 
little starch or glucose, but chiefly inulin and levulose, give rise in 
diabetes to a comparatively slight glycosuria, and the plants are not 
rare in kitchen-gardens even as far north as Stockholm, and over 
the greater part of Europe. Jerusalem artichokes are, to my taste, 
far inferior to potatoes, but they are certainly of some value to dia¬ 
betics, and, like potatoes, they constitute a good vehicle for butter. 
The tubers of Stockys affirm are chemically similar to Jerusalem arti¬ 
chokes ; but, at least in my country, they are quite small, and offer 
no advantages over the latter vegetables. 

With a more liberal diet one may give those vegetables that contain 
only a small amount of starch, but which contribute largely to 
the necessary variety and to the maintenance of the appetite. From 
the list at the end of this book it will be found that we have chiefly 
to keep to lettuce, spinach, cucumbers, young string-beans, celery, 
asparagus, radishes, mushrooms . Tomatoes, the different kinds of 
cabbage, almonds, and nuts, f and some fruits ( cranberries, strawber¬ 
ries) may often be allowed in small quantities. “ Sauerkraut ” has 
already been mentioned as almost always admissable when well 
fermented—unfortunately, many patients, after a short period of 
warm appreciation, acquire a loathing for it. We almost constantly 


* When younger, the tubers contain a considerable amount of starch and glucose. 

f Hazelnuts, walnuts, peanuts, Brazilian nuts, cocoanuts, are permitted, but not 
chestnuts. 





TREATMENT. 


277 


exclude everything containing more than eight per cent, of carbo¬ 
hydrate, except bread and potatoes, which must be weighed. Some¬ 
times, however, we allow a large baked apple at breakfast for the 
sake of its aperient quality. 

Of liquids, tea and coffee with saccharin or crystallose (see below) 
or levulose, or without any corrective at all, are permitted during the 
earlier part of the day except during periods of severe diet. A cup 
of tea of ordinary size contains about one gram, a cup of coffee about 
two grams, of carbohydrate. I constantly interdict the use of both 
of these in the evening on account of their disturbing influence on 
sleep, which is, at best, not very sound in diabetic patients. A 
glass of milk, or some alkaline water, or even a weak grog is a better 
ingredient of the patient’s supper or late dinner. 

Moderate quantities of red wines, European or American, may 
be allowed ; of white wines those from the Rhine are the best. 

Among alcoholic liquors, however, none is better for the dia¬ 
betic patient than cognac , brandy , whisky , gin , and similar drinks. 
These must be taken diluted, best with some carbonated mineral 
water, and the amount of alcohol they contain must not in the 
twenty-four hours exceed one-fourth, at the very utmost one-half, 
of a gram per kilo of bodily weight. 

All sweet wines,—champagne, port, Madeira, sherry, marsala, 
etc.,—“liqueurs,” and punches are forbidden under all circum¬ 
stances in cases of diabetes. 

It is also well to interdict absolutely porter, beer, and ales of all 
kinds. These contain a good deal of carbohydrates, are generally 
drunk in considerable quantities, if drunk at all, and are easily 
dispensed with. 

The usefulness of milk * for the diabetic patient is more difficult 
to decide, and to some extent is a matter of individuality. Milk 


* Some physicians forbid milk in all cases of diabetes—a position that may possibly 
be defended. Dr. Donkin has been unfortunate enough to recommend it skimmed as an 
exclusive food in cases of diabetes. This prescription can not possibly be defended, even 
if it did not include the skimming, which deprives the diabetic of a large part of the fat 
and leaves the carbohydrate. I have myself never prescribed the “ Donkin cure,” but I 
have several times seen it prescribed by others, with its necessarily signally bad results. 
An adult person requires about six liters of skimmed milk in order to secure the necessary 
amount of calories. This gives him nearly three hundred grams of lactose, and does 
not, in other respects, constitute the best kind of diet. 



278 


DIABETES MELLITUS AND GLYCOSURIA. 


contains nearly five per cent, of lactose, and can not be allowed at 
all during periods of rigid restriction of the diet; it ought never to 
be allowed in large or unlimited quantities in any case of diabetes. 
In all severe cases, however, and in many mild cases one may allow 
200 or 300 cu. cm. of unskimmed milk to be taken at supper. 
The sour milk, much in use during the summer in the north of 
Europe, in which the lactose is in large part changed into lactic acid, 
forms a most pleasant, wholesome, and popular article of food for 
the diabetic patient. At present there are other methods of remov¬ 
ing the greater part of the lactose from the milk ; when this can 
be done, the greatest objection to the use of milk in cases of diabe¬ 
tes (not belonging to the class of persons in whom dyspeptic symp¬ 
toms arise in consequence) is removed. 

Diabetic patients often are very thirsty and consume considerable 
quantities of drinking water. This is partly a result of the increased 
amount of sugar and of toxins in the blood, of nature’s attempt to 
eliminate these toxins as far as possible, and of the difficulty in 
providing the tissues with the necessary supply of water from the 
strongly sacchariferous blood. There is nothing so absurd that it 
can not be prescribed, and there are physicians who advise their 
diabetic patients to restrict themselves in the drinking of water. If 
this is done at all extravagantly, it tortures the patient, increases the 
diabetic and other deleterious substances in the blood, changes the 
working conditions of the heart, increases the dangers from too con¬ 
centrated secretions (gall-stones, urinary concretions, etc.), acts 
unfavorably on the nervous system, and in severe cases multiplies 
the danger of coma. The drawbacks of polydipsia are the disten¬ 
tion of the stomach and the increase in the work of the heart. 
Both of these effects are greatly diminished by the avoidance on the 
part of the patient of drinking large quantities at once. Diabetic 
patients should be advised to drink as much water as they like 
during the twenty-four hours, but to take the whole quantity in 
frequent small portions. Instead of ordinary water they may with 
advantage sometimes drink carbonated alkaline mineral waters. If 
the polydipsia is very marked, the patient may be spared a couple 
of hundred calories by heating the drinking water. 

Different substances on account of their sweet taste have lately 
been used as substitutes for sugar in cases of diabetes. The most 


TREATMENT. 


279 


common of these is (Fahlberg’s) saccharin (=anhydro-ortho-sulph- 
amin-benzoic acid). This substance, taken in amounts of a few 
centigrams every day, in the form of the small tablets to be had of 
druggists, sweetens tea and coffee or anything else with which it is 
used. I am not certain that I have ever observed the dyspeptic 
effects dwelt upon by Bernstein, v. Jaksch, and others. Small 
amounts seem harmless in this respect. The use of saccharin, 
however, causes the appearance of a reducing substance in the 
urine, and from this fact alone some influence on the kidneys might 
be suspected. The taste of saccharin is not pleasant, neither is the 
use of a sweetening substance very important to the patient ; most 
persons become indifferent in this respect. The antizymotic quality 
of saccharin is too weak to give it any distinct advantage in ordi¬ 
nary small amounts. I usually tell patients of saccharin and 
advise them to take as few tablets as possible daily; they then gen¬ 
erally use it for a time, and then without regret abandon it. Sucrol 
or dnlcin (=paraphenetol-carbamin) is in large doses a poison 
(Kossel, Aldehoff). I have not used it, though several writers 
affirm that they have seen no bad effects from small amounts. I do 
not know of crystallose more than its appearance and its taste, which 
latter is more pleasant than that of saccharin. Mannite causes 
diarrhea. 

Levulose has distinct nutritive value, increases the glycosuria 
but moderately, and has no other bad effects. It is, however, still 
too expensive for poor patients, and some persons take a dislike to 
it. 


An enormous and a significant number of “specific ” and other 
remedies have been used in the treatment of diabetes. Upon the 
whole, too much importance has been attached to any diminution 
in the hyperglycemia and glycosuria, however transitory, and 
too little consideration has been given to the first duty of every 
physician—viz., not to do harm. It seems almost incredible that 
there are physicians who recommend, e. g ., uranium nitrate for the 
purpose of decreasing the glycosuria, and it seems certain that even 
minimum quantities of this poison with its violently irritating 
effects on the alimentary canal and on the kidneys must in the 
course of an hour do more harm than considerable hyperglycemia 


28 o 


DIABETES MELLITUS AND GLYCOSURIA. 


will in the course of a week. The “specific” influence of many 
drugs may probably be only imaginary, and the diminution of 
hyperglycemia and glycosuria a result of impaired digestion. Even 
if this “ specific ” influence is real, its cost may easily be too great, 
and I believe it to be good advice to recommend the administration 
to diabetic patients of only such drugs as can certainly be taken for 
some time without serious detriment. Even the best “specific” 
remedies for diabetes are but very uncertain and weak in any 
“specific” influence, and the longer one has the opportunity of 
watching the effects of extolled remedies of this kind, the more 
skeptical does he become of their great value. 

Of some real, though not of great, specific value is opium , which 
has been used in the treatment of diabetes at least since the begin¬ 
ning of the nineteenth century. In many cases—but not in all—it 
distinctly diminishes the glycosuria and, what I consider to be much 
more important, it improves the patient’s general somatic and mental 
state. I prescribe it when I find a rapid diminution in the power 
of assimilation and during periods of nervous exacerbations ; under 
the latter condition it is really of decided value. One begins with 
small doses, increases them to quite considerable ones (from 8 to io 
centigrams—i to i y 2 grains—of pure opium per day for an 
adult), and after some time, perhaps days or weeks, gradually 
diminishes the dose, and finally withdraws the drug altogether. It 
is advisable never to use opium for any great length of time. 

As to codein , and still more as to morphin , these are in every re¬ 
spect much less valuable in cases of diabetes than is opium. Con¬ 
sidering the great danger to the patient of becoming addicted to 
them from the prolonged daily use of any of these remedies,—cer¬ 
tainly one of the worst of human miseries,—I think it the physician’s 
bounden duty, under all conditions, to reserve them for the mitiga¬ 
tion of transitory, severe pains or of perfectly hopeless conditions. 

When coma is present or there is imminent danger thereof, the 
administration of narcotic or hypnotic remedies is avoided as much 
as possible. 

Next to opium, arsenic may, perhaps, be mentioned as having some 
specific value in the treatment of diabetes. In some cases it does 
somewhat, though never to any large extent, cause a diminution in 
the glycosuria ; it may, perhaps, counteract the conversion of glyco- 


TREATMENT. 


28l 


gen into glucose and favor its transformation into fat in the liver, 
where, as has been mentioned, it in some way causes a diminution 
in the glycogen. It is, besides, as is well known, a splendid tonic, 
and in diabetic patients who are also anemic it may be given with 
great advantage. In my opinion one had better adhere to small 
doses, beginning with one and slowly increasing to three or four . 
drops of Fowler’s solution thrice daily, after meals, or giving a * 
corresponding amount of arsenic in pills (from gr. to gr. g-L-). 
After a couple of weeks the dose is slowly diminished. One may, 
in cases of diabetes, often with advantage combine arsenic with 
opium. 

The alkaline salts , especially sodium bicarbonate , have been 
used in the treatment of diabetes for at least since the time of 
Willis in the seventeenth century. They are believed to diminish 
the glycosuria, either by increasing the combustion of sugar in the 
tissues or by facilitating the storage of glycogen and counteracting 
the formation of glucose in the liver. The alkaline salts have dif¬ 
ferent merits (see below) ; but their power of diminishing glycosuria 
is exceedingly slight, and, unless large doses are given, conscien¬ 
tious investigation often fails to discern any decrease in the amount 
.of sugar excreted in the urine. Mialhe administered twenty grams 
of sodium bicarbonate a day, with the effect of diminishing the 
glycosuria somewhat; but such doses give rise to gastrointestinal 
disorders and weaken the patient. Richardiere gives it in doses of 
from four to ten grams a day for months ; but only periodically, 
and never in cases of pancreatic diabetes or in any case complicated 
by tuberculosis or by marasmus. Sodium bicarbonate is given 
chiefly in mineral waters, and then only in doses of a few grams 
a day, and the enormous doses are used by most physicians only 
in the presence of coma, or when there is manifest danger of it. 
The salts of tartaric, citric, phosphoric, lactic, benzoic, salicylic, hip- 
puric, and boric acids are also used, though far less than sodium 
bicarbonate. 

Ammonia , especially as carbonate and citrate, is also used, and 
has the merit of stimulating and of increasing the perspiration. 
Bouchardat recommends potassium carbonate and sodium and potas¬ 
sium tartrate for their powerful effect in eliminating uric acid. 
Clemens' solution contains potassium carbonate, arsenic, and bromids. 

19 



282 


DIABETES MELLITUS AND GLYCOSURIA. 


Calcium is for the moment and in some places popular in the 
treatment of diabetes. Grube gives his patients, four times a day, at 
meals, large doses of a mixture of seven parts of calcium carbonate 
and one part of calcium phosphate. These salts do not influence the 
glycosuria, but they are said to improve the general state and to 
facilitate the ingestion of fat. Robin uses calcium phosphate and 
glycerin. Those who give their diabetic patients large quantities of 
milk often add calcium carbonate. Magnesium hydrato-carbonate 
and calcined magnesia are also used, especially in cases with hyper¬ 
acidity of the stomach and constipation. Viau-Grand-Marais recom¬ 
mends strontium bromid; Martineau gives lithium carbonate (with 
arsenic). 

The alkaline and alkaline-saline spas are visited by large numbers of dia¬ 
betics. Carlsbad, Vichy, and Neuenahr enjoy at present the greatest repu¬ 
tation for their beneficial influence on diabetes. As a student of diabetes and 
as a practising physician in Carlsbad I have made it my purpose to acquire as 
correct an idea as possible of what may be reasonably expected for a diabetic 
patient from a sojourn of some weeks at one of these health-resorts. I consider 
it as great an advantage for these resorts as for the medical profession and for 
the patients that no false pretensions are supported and consequently no dis¬ 
appointments incurred, and that, on the other hand, the knowledge of the good 
results that undeniably are in many cases to be obtained is spread as far as 
possible. 

As for the glycosuria, Carlsbad and Vichy water, and doubtless, also, Neuen¬ 
ahr water in the moderate and rational amounts recommended at present, 
which scarcely ever go beyond a liter a day, have no appreciable influence, or 
one that is extremely slight and uncertain.* 

Does this mean that a course of treatment at Carlsbad, Vichy, or Neuenahr 
has no value at all for diabetic patients ? By no means. I feel safe in saying 
that most diabetic patients, especially in the mild stage, whom I or others 
have had occasion to observe in Carlsbad, have derived as considerable a 


* I protest, a priori , against any denial of this fact not founded on pure experimentation. 
I pass entirely over the naive reports on the influence of mineral waters on the glycosuria 
resulting from a simultaneous restriction of carbohydrates—they are not worth discussing. 
Neither will it do first to determine the supply of carbohydrate, and the amount of glucose 
excreted with the patient at home and occupied with his daily work, with its strains and 
emotions, and then to make the same determinations at the spa with the patient at leisure 
and subjected to the effect of other therapeutic agents than the mineral water. The 
experiment requires exact determinations of carbohydrate and glycosuria during two not 
too short periods, the one with and the other without mineral water, but both otherwise 
under as nearly similar circumstances as possible. Any one that undertakes the consider¬ 
able amount of work required in such an experiment will find that the glycosuria, 




TREATMENT. 


283 


benefit from their sojourn there as might be expected by any reasonable person. 
[We know that most laymen, and even some physicians, are not reasonable.] 
I do not consider the mineral water at Carlsbad, excellent as it is, to be the 
only or even the first therapeutic resource of the place. Still, the water has a 
good influence on dyspeptic symptoms, which are common in diabetic patients, 
as they are in others ; it also has a good influence on the constipation, which is 
equally common. It increases some of the secretions,—diabetic patients are, 
during its use, often less troubled by dryness of the mouth,—and I believe that this 
influence on the bile is of benefit in many cases. I am also willing to acknowl¬ 
edge the probability of some beneficial influence on the liver in other respects, 
and that an enlarged and tender liver becomes sometimes, under the use of 
the mineral water, smaller and less sensitive to pressure. Finally, I will not 
deny a favorable influence on gouty symptoms, which are very common in 
diabetics of the florid type in the mild stage of the dystrophy. The alkaline 
water must also have some slight neutralizing effect on the acidosis in the 
severe stage, though, according to my opinion, only a comparatively small 
number of patients in this stage do well in undertaking a journey of any length. 
It is, fortunately, not necessary to enter here into details with regard to the 
influence of the mineral water on the metabolic processes; but if it accom¬ 
plishes only what I have already acknowledged, it is well worth the drinking. 

The patient’s absence from home and its cares, his rest from intellectual 
work and mental worry, the hygienic and dietetic discipline, so much more 
easily enforced in a health-resort than anywhere else, and the other therapeu¬ 
tic resources available in such a place, are, in my opinion, together of much 
greater value than any mineral water, and it is these considerations that make 
up the enormous difference between a “ cure ” at home and the “ cure ” at a 
watering-place. The water, as it bubbles from the springs, or is contained in 
well-corked and well-preserved bottles, is, as every sensible person can under¬ 
stand, exactly the same. 

As I attach less importance to local mineral water than to other therapeutic 
agents, it is evident that in my choice between different health-resorts I shall 
be influenced less by the mineral water itself than by other circumstances, some 
of an individual and some of a local nature. 

There is, unfortunately, a single feature common to almost all advice in this 
respect recorded in the literature—viz., one always finds that the adviser 


cceteris paribus, with or without the use of mineral water, remains the same, or that the 
variations are no greater than they are without any appreciable external change whatever. 
Even in cases of simple glycosuria one finds with the use daily of a liter of mineral water 
that a faint trace of sugar, just large enough to cause a distinct reaction, remains as it 
showed itself before the use of the mineral water. In the different stages of diabetes one 
will arrive at the same results, though there may often remain some doubt as to the cause 
of small variations in the excretion sometimes observed even under apparently perfectly 
similar circumstances. This will be the case whether the mineral water is drunk imme¬ 
diately at the springs or from bottles ; if it were not, who would undertake to explain 
reasonably any possible difference ? Ivulz’s and all other serious investigations on this 
subject have led to the same results as my own. 




284 


DIABETES MELLITUS AND GLYCOSURIA. 


recommends, with rare exceptions, the sending of patients to the health-resort 
in which he is personally interested and is engaged in practice. The late Dr. 
Schmitz, who practised in Neuenahr, stated that, in order to avoid debilitating 
the organism, patients had better be sent to Neuenahr rather than to Carls¬ 
bad, whose waters, according to Schmitz, contain rather large amounts of 
sodium sulphate ; or to Vichy, where waters were said to contain rather large 
amounts of sodium bicarbonate. As it is always advantageous not to debili¬ 
tate the organism, these statements seem to mean that one must never send 
patients to Carlsbad or Vichy, but always to Neuenahr—and presumably (as 
long as he lived) to Dr. Schmitz. The French have no great regard either for 
Neuenahr or for Carlsbad, which latter place they, by the way, often believe to 
belong to Germany. “ II n’y a lieu d’ essayer Carlsbad que dans les cas ou 
une au deux cures a Vichy n’auraient pas donne de resultats satisfaisants.” 
The physicians of Carlsbad, on the other hand, think Vichy good only for 
amusement, and smile at mention of the 0.77 gram of bicarbonate which is 
the essential ingredient in a liter of the “ Augustenquelle ” in Neuenahr, and 
affirm that this latter place is dangerous for visitors on account of the risk 
of death from “the blues,” and that their own place, in point of therapeutic 
resources of all kinds, is the first health-resort that is, or was, or ever will be. 

I do not intend to offer like recommendations. I find it a difficult task to 
decide which of these superstitions is the sillier : the one that ascribes such a 
debilitating effect to the small quantities of alkaline sulphates, carbonates, and 
chlorids in Carlsbad,* or the one that attributes such wonderful effects to those 
salts or to the sodium bicarbonate at Vichy or Neuenahr ; and I am willing at 
once to acknowledge that many diabetic patients can derive benefits from a 
“ cure ” at any one of the three places named. I would, however, advise 
against sending thither patients in constant danger of coma, or suffering from 
tuberculosis, marasmus, or advanced arteriosclerosis, organic heart disease, or 
extreme senility. Fully developed mental disease also constitutes a contra¬ 
indication. 

The seeds of the Indian plant Syzygium jambulanum really in 
many cases diminish glycosuria; in other cases they seem not to 
have the slightest influence in that direction, whether the fluid ex¬ 
tract or the powdered seeds are used. Lewaschew administered 
from fifteen to thirty grams of the powdered seeds. I generally 
have given no more than ten grams, and have not observed any dys¬ 
peptic or other detrimental results. Fichtner saw the glycosuria 
increase after the use of the drug. Lepine and Barral believe that 
it increases both the production and the consumption of glucose. 


* The notion existing among laymen «fnd, in some degree, also among physicians of 
the debilitating influence of a course of treatment at Carlsbad owes its origin to the 
absurd system prevailing several decades ago in this Bohemian watering-place of giving 
patients enormous doses of the mineral water and of starving them half to death. 




TREATMENT. 


285 


Weil introduced the leaves of Vaccinium myrtillus L. (blue¬ 
berries) in the therapeutics of diabetes. The twigs, with the young 
leaves, are collected early in summer, when the bushes are in 
bloom. An infusion certainly causes diminution in the glycosuria; 
but at the same time it causes distinct dyspeptic disturbances. I 
have also heard patients complain of dyspeptic derangement after 
the use of Jasper’s pilulae myrtilli, and I have of late entirely ceased 
to use preparations of Vaccinium myrtillus L. 

Antifebrin , antipyrin , phenacetin , and exalgin have been recom¬ 
mended by French and other writers as “ specifics ” in cases of dia¬ 
betes. I should not prescribe any of these substances for any length 
of time. For the sake of the experiment, however, I gave one of 
my patients with an unvarying amount of glucose in the urine 
phenacetin at different times, and always with a distinct increase in 
the glycosuria. Lepine and Barral believe that antipyrin dimin¬ 
ishes both the production and the consumption of sugar. Even 
though it causes diminution in the glycosuria in cases in which 
there is increased production of glucose in the liver, I consider the 
patients better off without antipyrin or related substances. 

Quinin was used by Dobson more than a hundred years ago, and 
it is still recommended as a “specific” by Worms and others. It 
undoubtedly has a good influence in cases of glycosuria or diabetes 
due to malaria, of which several reliable instances have been placed 
on record. In other cases of simple glycosuria and diabetes I have 
failed to observe any influence on the excretion of sugar. 

The salts of bromin are excellent and comparatively innocuous 
remedies, and of great value in the presence of some neurasthenic 
disorders on account of their sedative action ; and they are often 
used in the treatment of diabetes. I have found it most advan¬ 
tageous to give them only once a day, in the evening, but then in 
rather large doses—not less than two grams. I prefer sodium 
bromid to potassium bromid. Neither the one nor the other salt 
exhibited any influence whatever on the excretion of glucose in a 
number of cases studied from this point of view. 

Among vegetable “ nervines,” valerian is the most recommended 
and is used especially often in France. It is said chiefly to diminish 
the polyuria. Bouchard administers ten grams or more of the 


286 


DIABETES MELLITUS AND GLYCOSURIA. 


extract per day; Lecoche from 0.30 to 0.50 gram; Dreyfus- 
Brisac from three to four grams with opium. 

Canna agra is used in America, but I know nothing of its value. 

Potassium iodid is used in the treatment of diabetes, as it is also in that of 
most other diseases. In some cases of diabetes complicated by syphilis I 
failed to observe any effect upon the glycosuria, even after the administration 
of large doses. 

Sampson recommends potassium permanganate by the mouth, in small 
doses, especially for anemic or lymphatic diabetics. Some French physicians 
believe that they have attained “ de grands succes curatifs ” with this remedy. 

Potassium bichlorate and potassium chlorate have also been used in the 
treatment of diabetes, and have shown their uselessness in this respect. 

Cantani, earlier in his career, praised lactic acid in the treatment of diabetes. 
It causes dyspeptic symptoms. 

Glycerin , introduced in the fifties by Basham, was for a time much used as 
a nutrient, chiefly on account of Schultzen’s theory of diabetes. It is now 
almost abandoned, less because Kiilz proved that it somewhat increases the 
glycosuria than because it causes gastro-intestinal catarrh. So much has been 
written on the subject that I feel unwilling to add more. If any one should be 
anxious to give it or to take it, he had better do so according to the following 
(French) prescription : Fifty grams of glycerin, one liter of water, five grams of 
citric acid ; to be drunk in the course of the day. 

Bouchardat tried and gave up inhalations of oxygen. Benzi trusted to 
ozone. Richardson produced with oxygen hydrogen dioxid in water and gave 
of this solution one-half ounce three times a day. 

I must not omit to mention the different ferments that have been recom¬ 
mended on various grounds in the treatment of diabetes. Pepsin does no 
harm. Yeast (of beer) would appear likely to do so in some degree, but 
according to Dr. Cassaet its action is .'perfectly marvelous, and the agent 
ought to be blessed by every diabetic patient. “ Son etat general se releve, 
son appetit renait, ses forces augment, ses donleurs s’attenuent son poids 
enfin se modifie,” which last means that the bodily weight may increase from 
three to eight kilograms in a fortnight. I have never used yeast in this way, 
and I feel certain that I never shall. Lepine saw the glycosuria diminish after 
subcutaneous injections of diastatic ferment (see below). 

Robin has devised a system of giving specifics. He begins by administer¬ 
ing antipyrin, one gram twice a day, for five days. Even he considers antipy¬ 
rin contraindicated by anorexia, albuminuria, marasmus, and autophagy, and 
to be useful chiefly in mild cases (“ diabete gras ”). Then for a fortnight 
he gives a mixture of arsenic, codein, and lithium [R. Sodii arsenitis, gm. 
0.002; Lithii carbonatis, gm. 0.12; Codeinae, gm. 0.02; Pulvis radicis Vale¬ 
rianae, gm. 0.25; Extracti chin, sin., gm. 0.40. One such powder is to be 
taken at breakfast and one at dinner, daily], with an interval of several days in 
the middle of this period. The treatment is concluded with opium, belladonna, 
valerian, quinin, bromids, alkalies, and cod-liver oil. “ Quid bonum faustum- 
que sit populo Gallico ! ” 


TREATMENT. 


287 

Theobromin has been used by different clinicians. Lindner’s “ glyco- 
solvol, put on the market as a specific in the treatment of diabetes, consists of 
theobromin-trypsin oxypropionate. 

Besides the substances mentioned, the greater number of the drugs of vege¬ 
table or mineral origin found in the Pharmacopeia have been used in the 
treatment of diabetes. As I consider all of these as worse than useless, I shall 
only mention some of them by name: Phosphorus, iodoform, uranium 
nitrate, alum, thallium sulphate, the salts of copper, the mineral acids, carbolic 
acid, creosote, thymol, benzosol, salol, naphtalin, balsam of copaiba or of 
Peru, tannic acid, rhatany, catechu, cubebs, piperazin, camphor, colchicum, 
santonin, belladonna and atropin, jaborandi leaves and pilocarpin, secale cor- 
nutum, and ergotin. The last remedy recommended, so far as I know, is 
methylene-blue (Pierre-Marie, Le Goff). 

Dismissing this long list from mind, we may devote a brief con¬ 
sideration to the proper use of mercury in cases of diabetes asso¬ 
ciated with syphilis. The diabetic organism is often more sensitive 
than others to poisons, and medical literature contains warnings 
against the too free use of mercury for antisyphilitic purposes with 
diabetic patients. As has already been mentioned, syphilis has in rare 
cases evidently been the cause of the diabetes by affecting in some 
way the nervous centers. If any reasons exist in such a case to sus¬ 
pect the presence of an active intracranial syphilitic process, there can 
be no doubt as to the physician’s duty to take almost any other risk 
than that of an undisturbed continuation of the local syphilitic process. 
Neither the modern large doses of potassium iodid nor anything else 
has shown itself as useful an antisyphilitic remedy as mercury, and I 
would not hesitate to administer it quite energetically in such a case 
in the manner that continues to be the best, the most efficient, and 
the least objectionable: viz., the old “inunction-cure,” with the 
usual precautions against mercurial poisoning. I have been gov¬ 
erned by the rule to assume any reasonable risk rather than to leave 
the organism a probable prey to syphilis in any case in which there 
is a mere accidental complication of syphilis and diabetes, whenever 
there is overwhelming reason to fear the presence of the first- 
named disease. Views on the subject of antisyphilitic treatment 
vary exceedingly even now, when the day of the antimercurial 
craze has passed. For myself, I treated my syphilitic patients more 
or less a la Fournier before I had ever read his work, and I believe 
in varying its details in diabetic cases only according to the rules 
that we follow in general. In my own cases of associated syphilis 


288 


DIABETES MELLITUS AND GLYCOSURIA. 


and diabetes the latter disease has been in the mild stage, and I 
have not observed any marked or peculiarly bad effects from the 
inunctions. 

Since thyroidin has yielded such good results in the treatment of 
myxedema, organotherapy (though with much less good results) has 
been applied to numerous other diseases, and also to diabetes.* 
Some physicians simply administer portions of pancreas, raw or 
slightly cooked. Others make an extract of the raw pancreas of 
sheep or oxen, which is finely cut and macerated for twenty-four 
hours in its own weight of (“physiologic”) solution of sodium 
chlorid or in glycerin ; this extract is later diluted with water. The 
filtered extract is afterward used in subcutaneous injection (Comby, 
Lancereaux, Gley, Thiroloix, Ausset de Cerenville, Battistini, etc.). 
Lepine macerates a pancreas in one liter of water, with one gram of 
sulphuric acid and five grams of malt-diastase, for two or three 
hours, at a temperature of 38° C. (100.4° F.). According to him, 
the diastatic ferment is thus changed into glycolytic ferment. Lepine 
then neutralizes the solution with sodium bicarbonate, and has the 
patient drink the whole in the course of twenty-four hours. This 
remedy is at least harmless. Lepine reports that he has observed 
from its use a decrease in the glycosuria and azoturia, an improve¬ 
ment in the general state, and an increase in bodily weight. Lepine, 
like all reliable observers, acknowledges that these results are 
highly uncertain. 

Spermin (Pohl) is praised by Eulenberg, Hofmeier, Hirsch, and 
others for its beneficial effects in cases of neurasthenia. Its prop¬ 
erty of increasing the alkalinity of the blood j* ought to add to its 
therapeutic value in severe cases of diabetes, in which something 
besides possibly might be expected from it, especially as regards 
neurasthenic symptoms. Spermin—which is said to exist to some 
extent in all organotlierapeutic remedies—has hitherto, so far as I 
know, never been used in its pure form in cases of diabetes. 


* Comby was, so far as I know, the first to employ this mode of treatment for 
diabetes. 

f As mentioned by Senator and by Loewy, but considered by Strauss not to be con¬ 
stant. 




TREATMENT. 


289 

Blumenthal makes subcutaneous injections of an extract of the 
live) and of the pancreas, and believes this to diminish the glyco¬ 
suria as much as forty per cent. 

Gilbert and Carnot administer an aqueous extract of the liver by 
the mouth or by the rectum,—“ opotherapie hepatiquef —and believe 
thereby to diminish the glycosuria. 

Thyroidin is sometimes prescribed in cases of diabetes by physi¬ 
cians of a hopeful and of an experimental turn of mind. 

Mechanotherapy , long neglected, has at last gained its proper 
position in many countries, and has also been used in the treatment 
of diabetes in the forms of both gymnastics and massage, partly on 
account of their quality of diminishing glycosuria, partly on account 
of other effects, in my opinion more important.* 

During the warm season I have found it most advantageous to 
prescribe gymnastics (z. e., systematic exercises) in the form of 
walks in the open air. When a diabetic patient passes from a 
sedentary life to one of moderate exercise, this, together with the 
usual effects on the appetite, circulation, functions of the bowels, 
and general state of health, also has some effect in diminishing the 
glycosuria. Fatigue has a contrary effect, and must be avoided, and 
the amount of exercise must be regulated in proportion to the 
patient’s strength, which in advanced cases often is quite small. I 
recommend two walks a day, and think it best for the first to be 
taken early in the morning and the last several hours before bed¬ 
time. A brisk walk just before bedtime, contrary to what is some¬ 
times asserted, has a disturbing influence on sleep. Next in value 


* I have set forth these effects extensively in my “ Handbook of Massage,” to which 
reference may be made. I can not enlarge upon the subject here, as this book on dia¬ 
betes has already grown beyond its intended limits. 

Exercise was prescribed in cases of diabetes mellitus in the' beginning of the present 
century by Marsch, and in more recent times it has been recommended by Bouchardat, 
Brouardel, Zimmer, Kiilz, and others. I have only recently had time to investigate the 
effects of general massage in diminishing glycosuria, having used it from time to time 
since Finkler and Brockhaus (1886) announced their results. While acknowledging 
the effect of energetic, prolonged general massage in causing diminution in the amount 
of sugar in the urine, I have not observed by far so good results as Finkler and Brock¬ 
haus, and do not consider a diminution from 450 to 120 grams of glucose to be possible 
as a result of mere massage. 



290 


DIABETES MELLITUS AND GLYCOSURIA. 


to a moderately brisk walk is horseback-riding. The bicycle, even 
apart from its liability to accidents, is less beneficial. 

In Scandinavian countries Zander’s medicomechanical institutes 
are highly popular in the larger cities during the winter, and they 
have spread from Sweden to a large part of the civilized world. 
Their purpose is to give gymnastics and massage (especially the 
different forms of tapotement) by machinery. Here in the North 
we consider them in many cases as excellent for giving “ mouvement 
cures” during our harsh winters; they are closed during the 
summer. Most of the patients suffer from weak heart or from con¬ 
stipation.* Gymnastics is now taught in all large communities, and 
can easily be arranged in homes without apparatus. 

The massage should be the “general,” with effleurage (stroking) 
frictions, petrissage (kneading), and tapotement (striking, vibrations) 
of the greater part of the body. The different groups of muscles 
of the limbs and of the trunk should be subjected to this treatment. 
Frictions of the abdominal wall over the colon, with their excellent 
influence on the functions of the bowels, should be carefully prac¬ 
tised in the way described by me and now known almost every¬ 
where. To exercise any influence at all on the glycosuria, and in 
order that its well-known beneficial influence may be exerted besides 
to any great extent, general massage must be practised for a full 
hour daily, preferably in two seances. Under these conditions gen¬ 
eral massage requires but little technical skill, and it may, after 
some instruction, be performed by any intelligent and available 
servant of the same sex as the patient. 

Hydrotherapy is of considerable value in cases of diabetes for its 
effect on the nervous system and on the skin. The diabetic patients, 
however, are always sensitive and must be protected against exces¬ 
sive temperatures, and, in general, the different forms of baths to be 
used in these cases vary from 20° C. (68.7° F.) to 36° C. (96.8° F.). 


* I shall entirely omit any description of the details of a “mouvement cure,” as 
carried out in Zander’s institutes or elsewhere, but will mention that, since I saw a 
similar treatment recommended by some Italian physicians and by Charcot, I have some¬ 
times, in cases of neurasthenic "sleeplessness, applied vibration to the head by means of 
Zander’s machines, and with surprisingly good results. The vibrations must be given 
with some force ; they are contraindicated by arteriosclerosis. 



TREATMENT. 


29I 


Different proceedings, constituting a mild cold-water- cure, are of 
considerable value. 

A sheet-bath is sometimes used and generally given in the morn¬ 
ing when the patient leaves his bed. A sheet wrung out of water 
at a temperature of about 20° C. (68° F.) is for a moment wrapped 
around the patient, who is then energetically rubbed with a dry 
sheet. 

I prefer to recommend to my diabetic patients another form of 
bath, often and daily used by healthy persons of the upper classes 
in many countries and by patients of different kinds. This bath is 
best taken in an ordinary sitz-bath , partly filled with water, which 
for sensitive persons may be kept at a temperature of about 20° C. 
(68° F.). The patient, on arising in the morning, sits down in the 
tub, squeezes the water out of a large sponge three or five times 
upon his neck, and afterward, while drying the upper part of his 
body, stands in the tub. The whole bath lasts little more than a 
minute. At its conclusion the patient either immediately dresses for 
a brisk walk or returns to bed for a few minutes, until the reaction 
following the bath is fairly started. 

The half-bath, with gradually lowered temperature, is an excellent 
measure which I often prescribe for diabetic and for neurasthenic 
patients in Carlsbad. The patient sits in a large tub half filled 
with tepid water (from 30° to 35 0 C.—from 86° to 95 0 F.) which, 
for a little while, is thrown upon his chest and his back. Cold 
water is then added, and the patient for some few minutes is sub¬ 
jected to energetic rubbing of the greater part of the body. A 
moderately cold douche or a dip in a moderately cold pond ends 
the bath. 

Douches may also be used alone. They should be begun with 
tepid water, the temperature being gradually lowered to as low a 
degree as the patient feels able to endure, and the whole operation 
lasting not longer than about a minute. 

Sea-bathing or lake-bathing is to be recommended only in mild 
cases of diabetes. It should be indulged in only when the temper¬ 
ature of both the air and the water is comparatively high and with 
precautions against taking cold. Under these conditions sea¬ 
bathing, in my experience, presents no dangers and exerts its usual 
beneficial influence. 


292 DIABETES MELLITUS AND GLYCOSURIA. 

The tepid bath at about 35 0 C. (95 0 F.) can also be used by 
diabetics. It should last about a quarter of an hour and ought to 
be followed by a moderately cold douche. If taken in the evening 
to promote sleep, the bath may be given for half an hour at a tem¬ 
perature of 36° or 37 0 C. (96.8° or 98.6° F.), and it should not 
be followed by any cold-water application. 

The electric bath , moderately cold or tepid, and the bath in car¬ 
bonated water, are both of some value on account of their stimulating 
effect. 

The warm bath (at 38° C.—100.4° F.—or more) should be given 
diabetic patients only in the presence of incipient coma, and it ought 
to last about ten minutes. 

The addition of different salts, extracts, etc., to the bath is often 
pleasant to the patient and may be of some benefit to the skin. 

Electrotherapy is employed in cases of diabetes in the same way as 
it is in nervous diseases. It is generally the diabetic patient’s neuras¬ 
thenia or neuritis that necessitates the application of general or local 
galvanization or faradization. Like almost all forms of treatment, 
this has also been sometimes considered as diminishing the glyco¬ 
suria ; D’Arsonval lately mentioned such a result from the use of 
Tesla’s apparatus. 

Many causes combine to make the tissues of the diabetic patient 
a poor soil for healing processes. The deleterious effects of hyper¬ 
glycemia and blood-toxins, of weak heart, of arteriosclerosis, of the 
diabetic endarteritis in the small vessels, and of defective nervous in¬ 
fluences have already been mentioned. The patient’s neurotic tem¬ 
perament often adds alcoholism to his other drawbacks. Suppurat¬ 
ing and septic processes and hemorrhages are more common among 
diabetics than among others. The different physiologic phases of 
the healing process, both in the soft and in the bony tissues, 
take place with less energy than usual. The surgeon, ready for a 
needed operation, has often replaced his knife on discovering sugar 
in his patient’s urine, fearing to operate in a case of diabetes, and 
knowing that he would incur less responsibility by abstaining from 
than by engaging in an unsuccessful operation. Many a surgeon 
has thus been saved, and many a diabetic patient who might have 


TREATMENT. 


293 


been saved by surgery has been sacrificed. In the sixties, however, 
antisepsis and asepsis, and the works of Griesinger, Marchal de 
Calvi, and others on the surgical complications of diabetes began 
to remove timidity of operating under such conditions. We owe 
a good deal to the French in this connection, though surgical 
nihilism in diabetes has had its advocates also in France (Landouzy, 
Palle, and others). The superstition against operating in cases of 
diabetes no longer prevails, and statistics prove that even such deli¬ 
cate operations as those on the eyes have almost as favorable an 
outlook in the presence of diabetes as in its absence. 

Operations on diabetic patients should, if the circumstances 
permit, be preceded by a course of preparatory treatment. In the 
mild stage the hyperglycemia should be removed for a couple of 
weeks previous to the operation, and the carbohydrates be with¬ 
drawn from the food until glycosuria disappears, if no urgent 
reason, as set forth on a preceding page, to the contrary exists. In 
the severe stage the acidosis is to be feared more than an increase in 
the constant and inevitable hyperglycemia, and consequently a fair 
supply of carbohydrates may be allowed. Alcoholic and other bad 
habits are to be strenuously, but wisely, corrected during this time. 
The general state is improved by all reconstructive remedies, by 
iron and arsenic when anemia is present, by nutritious, easily 
digested food, by general massage, etc., in all cases. 

Asepsis is to be preferred to cmtisepsis in operating in cases of 
diabetes as soon as the preparation of the skin is ended, on account 
of the irritating influence on the diabetic’s sensitive tissues by anti¬ 
septics and of the patient’s greater susceptibility to the action of 
poisons. 

Another rule among surgeons, in case of diabetes, is to prefer the 
thermocautery to the knife, as soon as there is a choice between the 
two, the better to avoid hemorrhage (and infection). 

Diabetic gangrene , which occurs in about ten per cent, of all cases 
of diabetes (Griesinger), necessitates operations more often than 
any other complication, especially upon the lower limbs. In many 
cases diabetic and senile changes combine to make the general state 
poor. In other cases, however, diabetic gangrene may exist 
despite an amazingly good general state of health. It is often pos¬ 
sible to bring about healing by the usual local (and general) treat- 


294 


DIABETES MELLITUS AND GLYCOSURIA. 


ment and to save the limb.* Surgeons recommend dry bandages 
in such cases. If operation becomes necessary for diabetic gangrene 
in the lower part of the limb, it is usually performed above the knee. 
Operation at the knee-joint is rarely performed, surgeons demand¬ 
ing a better state of health and better coverings than are generally 
possessed by diabetics. Godbe recommends operation above the 
knees in all cases with arteriosclerosis.f In diabetic patients with 
gangrene in the lower part of the leg thrombosis is quite common 
at the point of division of the popliteal artery, and operation above 
the knee is then necessary. 


* Constantin Panel has recently reported a case of diabetic gangrene in the lower 
part of the leg in which a cure was effected by means of a permanent bath of oxygen, 
removing the india-rubber apparatus twice a day in order to wash the gangrenous part 
with a warm solution of chloral (4 : 1000), by giving arsenic and lithium benzoate, 
and by enforcing strict diet. 

| As illustrated in one of my cases, the operation below the knee may sometimes 
yield good results even in the presence of distinct arteriosclerosis. 


ERRATA. 

On page 56, seventh line from bottom of page, “other plausible explanations” should 
read “ other plausible explanations than the mere deficiency of oxidation.” 

On page 153, fourth line from bottom of page, “ 18 grams of nitrogen ” should read “ 38 
grams of nitrogen.” 

On page 227, after the paragraph on acidosis, the following most important sentence has 
been omitted: “ The alkalescency of the blood may sink to T x ff of its normal value, 
but is never entirely annihilated.” 



TABLE OF THE COMMONEST KINDS OF FOOD, 
SHOWING CONSTITUENT PERCENTAGES OF 
PROTEID, FAT, AND CARBOHYDRATE.* 


SIMPLE ANIMAL FOODS. 

Proteid. 

Fat. 

Carbo¬ 

hydrate 

Meat, raw (of mammals),. 

15-22 

1 - 5-34 

_ 

Meat, cooked (roast, boiled, etc.),. 

34 

4 - 5-12 

— 

Meat, beef (smoked),. 

27 

15-5 

—■ 

Bacon, raw, . 

10 

5 ° 

— 

Lard, . 

o -3 

99 

— 

Meat-powder (dried),. 

75 

— 

— 

Chicken, raw, . 

20 

4 

— 

Pigeon, raw, . 

Duck (wild), raw,. 

Fish, fat (salmon, eel), raw,. 

22 

1 

— 

22.5 

3 

— 

15-20 

7.5-28 

— 

Fish, lean (cod, pike), raw,. 

15-20 

1 

— 

Stock fish, dried (cod), . . 

80 

1 

— 

Oysters, . 

5 

o -3 

2.6 

Eggs, . 

13 

11 

— 

Eggs, white of, . 

12 

o -5 


Eggs, yolks of, . 

16 

32 


Caviar, . 

32 

14 

4.8 

Milk, . 

3-5 

3-6 

Milk, skimmed, . 

3-5 

0.6 

4.8 

Cream, . . 

3-5 

20 

3-5 

Whey, . 

o -3 

0.2 

5 

Butter, . 

0.8 

83 

— 

Cheese, rich,. 

27 

30 

2-5 

Cheese, .-. 

35 

4 

2 


X 

5-30 

— 

MIXED ANIMAL AND VEGETABLE FOODS. 




Omelet of eggs, cream, and ham,. 

15-5 

19 

1 

Omelet of eggs, cream, and flour (pancakes), .... 

12 

10 

25 

Waffles J of cream, flour, and water (Swedish style), . 

10 

12 

25 

Sausages, in general,. 

17-27 

26-40 

0.-5 


12 

n -5 

25 


16 

26.5 

6.5 


10 

12 

11 


*The figures are chiefly taken from Konig’s well-known work, in part from the 
publications of Munk and Ewald, Jurgensen, and others. The table has been piepaied 
with a view to conciseness, but it will enable the physician to form an idea as to the 
caloric value of almost any kind of food. 

f Liver, as prepared for the table, contains only a small percentage of glycogen. 

J Waffles, Swedish style, when made exclusively of cream, flour, and water, usually 
contain about twenty-five per cent, of carbohydrate ; but they are extremely voluminous 
and light and form a good substratum for butter with a comparatively very small supply 
of carbohydrate. Except when a rigid diet is to be observed, they can sometimes be used 
by diabetics instead of bread. 


295 


















































296 


DIABETES MELLITUS AND GLYCOSURIA. 


1 


SIMPLE VEGETABLES AND FRUITS (Uncooked). 

Proteid. 

Fat. 

Carbo¬ 

hydrate. 

Jerusalem artichokes (topinambour).. 

2 

O. I 

15.2* 

Lettuce,. 

1.4 

°-3 

2.2 

Cucumbers, . . .. 

I 

0.1 

2-3 

Asparagus,. 

1.8 

0.2 

2.6 

Spinach,J. 

3 

0-5 

3-5 

Radishes,... 

1.2 

0.1 

3-8 

Celery (leaves),. 

4.6 

0.8 

10 

Onions, . 

2.7 

o -3 

6.5 

Mushrooms (agaricus),. 

3-6 

o -3 

6.8 

Cabbage (white),. 

1.9 

0.2 

4.9 

Cauliflower,. 

2 -5 

°-3 

4-5 

Cabbage (green),. 

4 

0.9 

ii.6 

Cabbage (Brussels sprouts),. 

4.8 

°-5 

6.2 

Cabbage (red),. 

1.8 

0.2 

5-9 

Parsley, . 

3-7 

0.7 

7-4 

Tomatoes,. 

1.2 

0.3 

4.1 

String-beans,!. 

2.7 

0.1 

6.6 

Peanuts (Arachis hypogsea),. 

28.2 

46.4 

8 

Almonds,. 

24.2 

53-7 

7.2 

Walnuts,. 

16.4 

69.2 

7.9 

Hazelnuts,... 

15.6 

66.5 

9 

Cranberries, -... 

0.1 


1.5 

Raspberries,. 

0.4 

— 

5-3 

Currants (red and white),. 

o -5 

— 

6 -3 

Blueberries,. 

0.8 

_ 

5-9 

Strawberries,. 

0.9 

_ 

3 - 4-4 

Gooseberries,. 

0.5 

_ 

8.4 

Plums,. 

0.4 

— 

8.2 

Cherries,.. 

0.7 

— 

12 

Apples,. 

0.4 

— 

12 

Pears, .. 

0.4 

— 

11.8 

Oranges (juice),. 

0.4 

— 

5-54 

Peaches,. 

0.65 

— 

11 .5 

Bananas,. 

1.9 

0.6 

23 

Grapes,. 

0.6 

— 

16.3 

Carrots, . 

1 

0.2 

9.4 

Turnips,. 

2.1 

0.1 

11.7 

Potatoes,... 

1.8 

0.2 

20.6 

Sweet potatoes,. 

1.3 

0.3 

23 

Beans (seeds, dried),. 

24.3 

1.6 

49 

Peas (seeds, dried),. 

22.8 

1.8 

52.4 

Apples, dried,. 

1.3 

0.8 

59-8 

Pears, dried,. 

2 

0.3 

58.8 

Prunes,. 

2.2 

o -5 

62.3 

Raisins,. 

2.4 

0.6 

62 

Figs,. 

5 

— 

45-3 


,v The carbohydrate in the Jerusalem artichokes consists of inulin, levulose, and gum. 
They are thus especially suitable for the diabetic’s table. In many fruits the carbo¬ 
hydrate consists partly of levulose in addition to starch and glucose. 

t The figures refer to the green leaves of Spinacia oleracea—not to spinach prepared 
with flour. 

t The figures refer to string-beans with full-grown seeds. Before the seeds are developed 
string-beans contain much inosite, but only an insignificant amount of true carbohydrate, 
and they are an important item in the diabetic’s bill of fare. 
































































PROTEID, FAT, AND CARBOHYDRATE IN FOOD. 


2 9 ; 


SIMPLE VEGETABLES AND FRUITS (Uncooked). 

( Continued .) 

Proteid. 

Fat. 

Carbo¬ 

hydrate. 

Chestnuts,. 

5-5 

1.4 

38.3 

Coffee (burnt),. 

12.2 

12 

13-4 

Tea (dried leaves),. 

21 

3-6 

17.6 

Chocolate, unsweetened,. 

5 

15.2 

74.8 

Chocolate, sweet, . 

12.3 

52.3 

28.3 

CEREALS,^BREADS, ETC. 




Rice, dried,. 

9 

0.8 

88 

Sago, dried,. 

0.8 

— 

86.1 

Indian corn (maize),. 

11.67 

5-5 

77.8 

Macaroni, dried,. 

9 

0.3 

76.7 

Flour of the Soya-bean,. 

3-4 

16.4 

29.6 

Rye-flour,. 

12.8 

2-3 

81.3 

Wheat-flour, . ’.. 

10.5 

1.3 

87.1 

Oatmeal, dry (coarse),. 

15 

6 

64.73 

Rye-bread,. 

6.1 

0.4 

49.2 

Wheat-bread,.. 

6.1 

0.4 

5 i 

Graham bread, . 

6 

°-3 

39-41 

English biscuits,. 

7.2 

9-3 

75 -i 


LIQUORS. 

Alco 

Percei 

Vol. 

HOL. 

SITAGE. 

Weight. 

Sugar 

and 

Extract. 

Cognac, French brandy,. 

55 

47-3 

0.6 

Whisky, American,. 

60 

52.2 

— 

“ Scotch, . 

50-3 

42.8 

— 

“ Irish,. 

49.9 

42.3 

— 

Cider,. 

— 

4.2 

8 

Beers and ales,. 

— 

2. 5 - 4-9 

4-7.2 

Porters, . 

— 

5-3 

8.9 

Rhine wines, white,. 

— 

11.4 

2.6 

Rhine wines, red,. 

— 

10 

3-4 

Beaune (Burgundy),. 

9 

— ’ 

2.7 

St. Emilion (Bordeaux), . 

8.7 

— 

3 

Swiss wine, white,'. 

9.6 

— 

i -9 

Swiss wine, red,. 

9.4 

— 

1.6 

Austrian wine, red,. 

9-5 

— 

2.7 

Sherry,. 

— 

17 

5 

Madeira,.. 

— 

15.6 

8.6 

Marsala,. 

— 

16.4 

8 

Port wine,. 

— 

16.4 

10.2 

Malaga, . 

— 

11 5 

30-3 

Champagne, . 

— 

9 

24.8 

Curacao,. 

55 

— 

57 

Arrac-punch (Swedish),. 

26.3 


69.8 


19 









































































PERSONAL REGISTER. 


A. 

Abeles, 26, 38, 65, 177, 178, 186, 252 

Abelmann, 105, 167 

Achard, 60, 243 

v. Ackeren, 129, 135, 209 

Acri, 117 

Aladoff, 34 

Albertoni, 116, 117,133, 223 
Albic, 220 
Aldehoff, 165, 279 
Althaus, 90, 94 
•Amann, 219 
Ambrosiani, 10 
Andral, 49, 55, 159 
Anger, 98 
Anselme, 138 
Anstoots, 63 

Araki, 13, 51, 56, 57, 58, 68 

Argutinsky, 186 

Armanni, no, 113, 116 

Arnschink, 171 

Arthaud, 33, 48, 49 

Arthur, 49 

Arthus, 180 

Asher, 32 

Auche, 94, 97 

Auerbach, 94 

Ausset de Cerenville, 288 


B. 

Baisch, 26 
Barlow, 36, 62 

Barral, 181, 188, 191, 192, 284 

Basham, 286 

Battistini, 288 

Baum, 37 

Baumann, 217 

Beale, 63 

Becker (O.), 119, 120 
Begbie, 41 

Bence Jones, n, 13, 26, 159 
Benda, no 
Benzi, 286 
Bequerel, 35, 36 
Beranger-Ferand, 15 


Berger, 119 

Bernard, Claude, 11, 13, 24, 29, 31, 33, 
49. 54. 57. 66, 67, 105, 169, 173, 176, 
183, 191, 203, 216, 229 
Bernstein, 279 
Berthier, 87 
Bettman, 36, 102 
Bial, 170, 180, 182 
Bidder, n 
Biedl, 243 
Biefel, 56 
Bischoff, 11, 171 
Bischofswerder, 216 
Blair, 18 
Blake, 54 
Blau, 82 
Bleibtreu, 235 
Bleile, 170, 181 
Blocq, 36 
Blot, 65 

Blumenthal, 289 

Boccardi, 97, 108, 113, 116, 117, 177 

Bock, 53, 58, 181, 187 

Boecker, 229 

Boedeker, 217 

Bohm, 34, 38, 68, 176, 181 

Bollinger, 50 

Bond, 35 

Bonome, 113 

Borchert, 229, 232 

Bordier, 62, 63 

Bose, 17 

Bouchard, 12, 14, 53, 55, 74, 76, 9 1 . 

119, 120, 135, 228, 284 
Bouchardat, 12, 13,203, 216, 267, 281, 
286 

Bouchut, 62 
Bouveret, 121 
Brault, 137, 177 
Bremer, 101, 244 
Breul, 26 
Brieger, 133 
Brietzke, 186 
Bright, 105 
Brockhaus, 203, 289 
Brogniart, 216 




300 


PERSONAL REGISTER. 


Brouardel, 37, 193, 289 
Brown-Sequard, 191 
Briicke, 11, 26 
Brunelle, 53, 54 
Brunner, 135 
Buchheim, 171 
Budde, 115, 216 
Budge, 34, 200 
Bull, William T., 105, 135 
Bunge, 170, 185, 217 
Burdel, 64 
Burger, 231 
Burghardt, 68 
Burns, 94 
Bury, 90, 94 
Bussenius, 203 

Butte, 33, 34, 48, 49, 182, 183, 192 
Buzzard, 90, 94 


C. 

Calmette, 18, 64 

Camplin, 274 

Cantani, 12, 14, 41, 77, 267 

Cantlie, 18 

Caparelli, 165 

Carnot, 289 

Caroe, 16 

Carrion, 138 

Cartier, 53, 54 

Casal, 57 

de Cassaet, 286 

Cavazzani, A., 35, 183 

Cavazzani, E., 35, 183 

Celsus, 10 

Charcot, 24, 63, 90, 94, 97, 216, 257 
Charrin, 129 
Chauffard, 137 

Chauveau, 12, 32, 33, 49, 165, 166, 
^ 181, 185, 186, 189, 194-198, 229 
Chittenden, 54, 182 
Chvostek, 36 
Coignard, 52, 216 
Colasanti, 218 
Colenbrander, 192 
Colrat, 49 
Comby, 288 
Coolen, 60, 61 
Coranda, 133 
Cornevin, 62 
Couturier, 49 
Cowley, 135 
Cramer, 66 

Cremer, 60, 174, 175, 185 
Crichton-Browne, 87 
Cruikshank, 10 
Cunningham, 36 
Curee, 54 


Cyon, 34 
Czapek, 208 


D. 

Dalton, 180 
D’Arsonval, 292 
Dastre, 49, 56, 179, 192 
Davis, N. S., 81 
Davy, 101 
Decker, 63 
De Dominicis, 165 
Deichmiiller, 133 
De Jong, 35, 200 
Delamare, 60 
Demant, 57, 176 
Demme, 35 
Derignac, 219 
Deutschmann, 119, 120 
Devie, 113, 219 
Dickinson, 96 
Dieulafoy, 128 
Dittrich, 108 
Dobson, 10, 77, 284 
Doch, 57, 174 
Donkin, 277 
Dreyfus-Brisac, 286 
Dufour, 183 
Dufresne, 58 
Dujardin-Beaumetz, 127 
Dumontpellier, 36 
Duponc, 34 
Duponchet,£64 
v. Dusch, 76, 131 


E. 

Ebstein, 12, 14, 37, 86, 116, 117, 
216 

Eckhard, 32, 33, 55, 57, 58 
Edel, 187 

Edwards, Mile. Blaine, 35 
Ehrlich, 117, 177, 178 
Eichhorst, 63, 66, 94, 97, 98 
Eliotson, 105 
v. Engel, 215 
Engelmann, 231 
Erlenmeyer, 91 
Ernst, 115 

Eulenburg, 35, 55, 288 
Ewald, 51, 58, 178, 181, 187, 295 
Exner, 49 


F. 

Fahlberg, 279 
Falkenberg, 38 
Feilchenfeld, 54 


175 , 







PERSONAL REGISTER. 


301 


Fere, 36, 133 

Ferraro, 97, 100, 108, 113, 116 
Fichtner, 116 
Fick, 186 

Finkelstein, 229, 232 

Finkler, 37, 135, 203, 289 

Finlayson, 86 

Finn, 174 

Fischer, 37, 62 

Fitz, no 

Fleiner, 134 

Fleischer, 57 

Fles, 105 

Fleury, 98 

Flint, 186 

Fodor, 129 

Foerster, 119 

Forsell, 268 

Foster, 203 

Fraentzel, 175 

Frank, Peter, 64, 78 

Franque, 158 

Frazer, 34 

Frerichs, n, 12, 34, 35, 36, 52, 54, 55, 
56, 62, 63, 69, 93, 96, 98, 105, 108, 
1 17 , I 3 F 132, 172, 176, 1 77 , 188 
Freund, 58, 190 
Fiirbringer, 77, 103, 218, 229 
Futterer, 96 


G. 

Gabritschewski, 178 

Gaglio, 57, 165 

Gallard, 137 

Gans, 37, 104, 180 

Gara, 63 

Garofalo, 57 

Garrod, 76 

Gascuel, 83 

Gathgens, 229, 231 

Gaudard, 118 

Gelmo, 62 

Geppert, 52 

Gerhardt, n, 133 

Gerhardt, D., 102, 212, 227 

Geyer, 237 

Gianturco, 113 

Gib, Paul, 37 

v. Gieson, 117 

Gilbert, 289 

Gilles de la Tourette, 257 
Girard, 182 
Giron, 81 
Glenard, 111 

Gley, 60, 62, 165, 229, 288 
Gmelin, 10, 54 
Godlee, 294 


Goerlitz, 120 
Golowin, 49 
Golz, 52 
Goodhart, 96 
Goolden, 36, 63, 158 
Gorup-Besanez, 208 
Grsefe, 119 
Graf, 54 
Graham, 17, 61 
Graser, 62 

Griesinger, 12, 25, 36, 102, 293 
Grohe, 178 

Grube, 19, 76, 114, 282 
Gruber, 207 
Gubler, 63 

Guckelberg, 215, 230 
Gueneau, 63 
Gueudeville, 10 
Guiard, 115 
Guignard, 129 
Guinon, 93, 94 
Gull, 107 
Gumpertz, 88 
Giirtler, 57 


H. 


Habershon, 69 
Hale White, 207 
Haller, 135 
Hallervorden, 133 
Hammarsten, 170, 215 
Hammerschlag, 101 
Hanot, 113, 137, 138 
Hansemann, 110 
Harden, 127 
Harley, 49, 55 
Hartge, 116 
Hartsen, 105, 106 
Hartz, 216 
Hasse, 56 
Haughton, 229 
Haycraft, 207 

Hedon, 32, 120, 165, 166, 193 

Heidenhain, 81 

Heine, 159 

Heinemann, 109 

Heintz, 63 

Heller, 170 

Henrat, 98 

Henriot, 235 

Hensay, 97 

Hensen, 181 

Hergenhahn, 49, 173, 174, 176 
Hernandez, Gonsalez, 137 
Heyneman, Newton, 185 






302 


PERSONAL REGISTER. 


Heyse, 207 
Higgins, 32, 74 
Hirsch, 288 

Hirschberg, 119, 122,226 
Hirschfeld, 105, 170, 213 
Hodgkin, 81 
Hoesslin, 14 
v. Hoesslin, 94 
Hoffmann, 55, 220, 252 
Hoffmann, G. A., 12, 34, 38, 53, 58, 
176, 181, 187, 214 
Hofmeier, 288 

Hofmeister, 24, 30, 65, 67, 171, 200, 
203 

Holmgren (E.) 219, 237 
Holsti, 65 
Honigmann, 104 
Hoppe, 173 

Hoppe-Seyler, 52, 177, 190 

Horner, 121 

Huber, 50 

Hubner, 180 

Hiibner, 15 

Huchard, 35 

Hugonenq, 52, 219 

Hundhausen, 275 

Hunt, W., 81 

Huppert, 14, 63, 177 

Husband, 29, 66 


I. 

Ingerslev, 159 
Irisawa, 56 
Isenflamm, 159 
Israel, 100 


J- 

Jaccoud,14 
Jacobson, 119 
Jacobson, Otto, 64 
Jacoby (New York), 86 
Jacoby (Strassburg), 58, 69 
v. Jaksch, 53, 57, 101, 133, 215, 217, 
226 

James, A., 101, 131 
Jasper, 285 
Joffroy, 97 
Johannowski, 65 
Johnson (St.), 217 


K. 

Kahler, 30, 31, 35, 56 
Kaiser, 210 
Kalm, 219 


Kalmus, 97 
Kaltenbach, 65 
Kaposi, 81, 127 
Kassel, 215 
Kassowitz, 129 

Kaufmann, 12, 32, 33, 49, 165, 166, 
167, 181, 185, 189, 194-198, 229 
Kausch, 69, 165, 174, 175, 179 
Kemmerich, 214 
Kessler, 53 
Kinnicutt, 158 
Kirchner, 124 
Kirmisson, 83 
Kirsten, 65 
Kisch, 66 
Klebs, 34 

Klemperer, 58, 60, 67, 69, 115, 207 

Knies, 119, 120 

Kobner, 170 

Konig, 121, 295 

Koninck, 59 

Korner, 124 

Kossel, 279 

Kowalewski, 54 

Kratschmer, 24, 177, 229 

Kraus, 36, 192, 243 

Kraus, I., 79 

Kravkow, 215 

Kuhn, 124 

Kiihne, 26, 31, 177 

Kiilz, E., 17, 30, 33, 34, 38, 52, 53, 
132, 133, 157, 159, 170, 175, 176, 181 
203, 205-209, 213, 224, 229, 230 
Kumagawa, 185 
Kunkler, 36 
Kuntzel, 53 
Kupper, 172 
Kussmaul, 54, 131, 133 


L. 

Laache, 36 
Laborde, 158 
Lallier, 35, 36 
Lamanski, 34 
Lambert, 54, 182 
Lancereaux, 36, 108, 135, 288 
Landouzy, 293 
Landwehr, 219 
Lang, 66, 179 
Langendorff, 57,^165 
Lapique, 138 
Laseque, 107 
Laub, 53 
Laulanie, 235 
Laves, 176, 235 
! Lavoisier, 11 





PERSONAL REGISTER. 


303 


Leber, 119, 122, 123 
Leblanc, 15 
Lecanu, 102, 212 
Leconte, 54 

Lecorche, 14,94, 9$, 100, 286 
Le Goff, 287 
Legroux, 39 

Lehmann, 11, 67, 181, 214, 217 
Leichtentritt, 97 
Lemaire, 65, 219 
Le Nobel, 105, 134, 135, 209 
Leo, 209, 220, 235 

Lepine, 12, 33, 58, 69. 95, 165, 181, 
190, 191, 193, 220, 284, 288 
Leroux, 157, 159 
Letulle, 137, 203 
Leube, 178, 219, 229 
Leudet, 35 
Leval-Piquechef, 94 
Levene, 61 
Lewaschew, 284 
Lewin, 54 
Levin, 171 
Leyden, 90, 94, 97 
Lichtheim, 134, 221 
Liebig, 11, 174 
Lindemann, 175 
Lionville, 57 
Livierato, 232 
Loewy, 245, 288 
Lohnstein, 247 
Loye, 192 
Lubinoff, 98 

Luchsinger, 58, 172, 174 
Ludwig, 36, 187 
Liihdorf, 275 

Lusk, 60, 61, 170, 171, 181, 224 
Lussanna, 182 
Lustig, 34 


M. 

McDonnel, 38, 173, 182 
McGregor, 10 
Magendie, 11 

Magnus-Levy, 51, 115,235 
Maitland, 10 
Manchot, 51 
Mannkopf, 35, 67 
Maquenne, 207 
Marcet, 14 
Marcus, 66 
Marcuse, 165 

Marechal de Calvi, 81, 293 
Marie, 94 
Marinesco, 36 
Marinian, 91 


Marklen, 103 
Marsh, 289 
Marthen, 116 
Martin-Damourette, 52 
Martineau, 282 
Masoin, 53 
Matrai, 190 
Mauthner, 122, 209 
May, 175 
Mayer, 52 
Meissner, 182 

v. Mering, 12, 51, 52, 53, 55, 59,60, 
61, 105, 135, 136, 164, 170, 174, 177, 
181, 185, 187, 188, 203, 229 
Mermod, 14 
Metroz, 192 

Meyer, Jacques, 35, 36, 100 
Mialhe, 281 
Michael, 35, 96 

Minkowski, 12, 38, 52, 105, 106, 133, 
135, 136, 164-168, 177, 193, 202, 
207, 223, 229 
Minnich, 134 
Minor, 97 

Miura, 185, 199, 200, 213, 224 
Montuori, 182 
Morat, 33, 34, 183 
Moriggia, 66 

Moritz, 26, 59, 60, 185, 200 

Morrison, 69 

Moscatelli, 217 

Mosler, 229 

Mosse, 182 

Mosso, U., 14 

Muller, Fr., 106, 115, 171 

Munck, 34 

Munk, 171, 184, 295 

Miinzer, 50, 53, 132, 133, 229 

Musculus, 170 


N. 

Nasse, 101, 210, 231 
Naunyn, 14, 29, 32, 35, 36, 37, 38, 50, 
52, 66, 69, 71, 94, 102, 103, 107, hi, 
115, 116, 118, 134, 174, 203, 216, 
268 

Nebelthau, 174, 175, 176 
Neisser, 177 
v. Nencki, 13, 174, 234 
Nesbi, 116 
Nettelbladt, 158 
Neubauer, 220 
Neumann, 28, 58, 98 
Neumeister, 182 
Neusser, 49, 102 



304 


PERSONAL REGISTER. 


Ney, 65 
Nicolas, 10 
Niedergesass, 157 
Niedieck, 33 
Nommes, 191 
Nonne, 91 

v. Noorden, 12, 58, 185, 224 
Nordenson, 121, 123, 149, 162 
Nylander, 26 


O. 

Obici, 116 
Ogden, 32, 74 
Ollivier, 35, 56 
van Oordt, 35 
Oppenheim, 35, 93, 186 
Oppler, 247 
Orth, 135 

Otto, 171, 172, 181, 187, 188 


P. 

Palle, 293 
Palma, 207 
Panas, 36 
Panel, 294 
Papanikolau, 119 
Paracelsus, 10 
Parkes, 186 
Parmentier, 138 
Parrot, 158 
Paschutin, 177 
Paton, Noel, 182 
Pautz, 170, 232 

Pavy, 12, 13, 19, 20, 32, 34, 36, 38, 52, 
61, 69, 159, 174, 178-183, 186, 190, 
215,275 
Peiper, 34 
Penzoldt, 57 
Percy, 98 

Pettenkofer, 11, 214, 229, 232 

Petters, 133 

Peyrot, 81 

Pfliiger, 174, 186 

Philipeaux, 63 

Pichon, 58 

Pick, 77 

Pickhardt, 187 

Pierre-Marie, 36, 137, 287 

Pincus, 34 

Pisenti, 116, 117 

Pitres, 82 

Poli, 62, 63 

Poliak, 56, 66 

Pollatschek, 52 


Popper, 13 

Praussnitz, 59, 60, 171, 177, 185 
Prevost, 63 
Price, 94, 97 

Prout, 63, 75, 218, 267, 274 
Purdy, 17, 19, 20 


Q- 

Quinquaud, 53, 189 


R. 

Rabuteau, 54 
Range, 64 
Raynor, 87 
Reale, 38 
Rebitzer, 68 
v. Rechenberg, 232 
v. Recklingshausen, 35 
Redard, 63 
Redon, 62, 157, 160 
Reich, 229 
Reichhardt, 219 
Reignault, 11, 186, 234 
Reiset, 11, 186, 234 
Reynoso, 28, 53, 63 
Richardiere, 35, 37, 281 
Richardson, 35, 56, 120 
Riegel, 107, 108 
Rienzi, 38 
Riess, 216 
Ringer, 36 

Ritter, 55, 60, 182, 185 
Roberts, 159, 247 
Robin, 282, 286 
Roger, 59, 62 
Rohmann, 170, 208 
Rolf, 52 
Rollo, 10, 264 
Roos, 26 
Roque, 113, 219 
Rosenbach, 53 
Rosenbaum, 176 
Rosenblath, 82, 101 
Rosenfeld, 61, 226 
Rosenheim, 171 

Rosenstein, 57, 91, 94, 104, 108, 
Ross, 26, 90, 94 
Rossa, 66 
Rovere, 84 

Rubner, 11, 171, 172, 200, 232 
Rumpf, 133, 218, 227 
Rupstein, 230 
Ryndsjun, 34 



PERSONAL REGISTER. 


305 


S. 

Saikowski, 53, 57 
Salkowski, 175, 214 
Salomon, 172 
Samoje, 63 
Sampacchia, 113 

Sandmeyer, 97, 105, 165, 174, 177 
. Sauer, 56, 57 

Saundby, 17, 96, no, 113 
Savage, 87 
Scharlau, 36 
Schenk, 186, 188 
Schermetjewski, 13 
Schierbeck, 14 

Schiff, 13, 31, 32, 33, 36, 38, 56, 57, 182 

Schilder, 26 

Schindelka, 15 

Schindler, 77 

Schirmer, 119 

Schmidt-Rimpler, 119, 122 

Schmidt, G., 11, 181 

Schmitz, 20, 25, 49, 76, 115, 284 

Schultze, 14 

Schultzen, 13 

Schiitz, 35 

Schwarz, 168 

Schwiening, 180 

Scolozoboff, 54 

See, Germain, 60 

Seegen, n, 12, 29, 35,38, 58, 71, 118, 
171-178, 183, 186, 187,188, 194, 200, 
208, 275 
Segalas, 10 
Seitz, 105, no 
Semmola, 63 

Senator, 39, 55, 67, 84, 115, 159, 217, 
288 

Senff, 56, 57 
Senn, N., 105, 135 
Settenbom, 82 
Seyfert, 62 
Sieber, 13, 234 
Siebert, 36 
Siebold, 55 
Silver, 105 
Simons, 10 
Sinety, 65 
Smith, 35, 93 
Sobeiran, 10 
Socin, 174, 175 
Soldani, 35 
Sotniskewski, 177 
Souques, 93 
Spiegelberg, 65 
Spitzer, 192 
Spitzka, 35 

Stadelmann, 52, no, 133, 220, 227 
Startz, 216 


Steinhaus, 113 

Stern, 63, 157 

Stokvis, 173 

Strasser, 132, 133, 229 

Strassmann, 213 

Straub, Walther, 57 

Straus, 35, 37, 53, 58, 116, 234 

Straynowski, 118 

v. Striimpell, 37, 90 

Subbotin, 214 

Susruta, 10, 127 

Sydenham, 64 


T. 

Tangl, 49 
Taylor, 96 
Tcherinoff, 173, 174 
Tebb, 170 
Telz, 55 
Tenbaum, 231 
v. Terray, 63 
Teschemacher, 58 
Tessier, 25 
Thiel, 60 

Thierfelder, 229, 237 

Thiermesse, 15 

Thiroloix, 165, 166, 229, 288 

Tholozan, 18 

Thomas, 90 

Thompson, n 

Tiedeman, 10 

Tiegl, 180 

Toepfer, 58, 140 

Toll, 148 

Tollens, 133 

Topinard, 35 

Toralbi, 88, 202 

Trambusti, 116 

Traube, 11, 220 

Triboulet, 138 

Troye, 221, 228 

True, 120 

Tscherinow, 49, 173 


U. 

Uhle, 229 
Ulrich, 219 


V 


Vahl, 207 
Vamossy, 57 
Vas, 63 
Vauquelin, 10 


/ 







3°6 


PERSONAL REGISTER. 


Velisch, 38, 165 
Vergely, 94 
Verron, 95 
Vespa, 77 
Vetlesen, 240 
Viaud-Grand-Marais, 282 
Vogel, 219, 220 
Vogler, 36 
Voisin, 57 

Voit, 12, 170, 174, 210, 214, 229, 232 
Voit, E., 214 

Voit, Fr., 171, 174, 206, 207, 232, 243 
Voit, Hans, 34 
Vulpian, 63 


W. 

Wagner, 63 
Walkow, 217 
Walter, 52, 133 
Watson, 159 
Wedenski, 26, 209, 219 
Weichselbaum, 35 
Weil, 243 

Weintraud, 12, 104, 165, 179, 211, 221, 
234 

Weir-Mitchell, 84, 119 
Weiss, 174, 185 
Werther, 177 
West, 159 


Whitehouse, 54 

Wickham-Legg, 177 

Wiersma, 177 

Wiesinger, 119 

v. Wildt, 124 

Williams, 66 

Williamson, 97, 101, 245 

Willis, 10, 281 

Winogradoff, 57, 217 

Wislicenus, 186 

v. Wittisch, 49 

Wolf, 208 

Wolf berg, 174 

Wollaston, 10 

Wood, Horatio, 91, 127 

Worm-Muller, 26, 30, 46, 199, 200, 204 

Worms, 14, 284 

Woroschiloff, 173 

Woroschilski, 54 


Z. 

Zander, 257, 290 
Zenker, 103 
Ziemssen, 90, 94 
Zillesen, 56 

Zimmer, 13, 54, 68, 69, 191, 203, 208 
Zinn, 62 

Zuntz, 57, 62, 184, 186 



INDEX. 


A. 

Acetone, 61, 84, 133, 168, 214, 215, 
221 

Acetonuria, 168, 169 
Achroodextrin, 170 
Acid, acetic, 217 
butyric, 217 
carbonic, 56, 234 
dextronic, 52 

diacetic, 52, 53, 61, 133, 168, 214, 
221, 228 
formic, 215 
glycosuric, 217 

glycuronic, 51, 52, 179, 218, 239 
hippuric, 217 
homogentisinic, 217 
hydrochloric, 52 
lactic, 51, 52, 55, 57, 168, 179, 
218 

levulinic, 215 
mucous, 52 

orthro-n i t r o-phenyl-propionic, 
52 

oxalic, 52, 218 

/ 3 -oxybutyric, 52, 61, 133, 168, 
214, 221 
phloretic, 59 
propionic, 217 
prussic, 52 
salicylic, 52 
sugar, 52 
sulphuric, 52 

coupled (etherous, 
aromatic), 53, 59, 
172, 219 

in sulphates, 53, 172, 
219 

Acidity of gastric juice, 104, 108 
of urine, 219, 227 
Acidosis, 72, 168, 227, 263 
Acids, fatty, 52, 217 
Aciduria, 227 
Acne, 127 

Addison’s disease, 68 
Adiposity, 140 
Age, 19, 158 
Akromegaly, 36 


Albuminuria, 51, 52, 59, 76, 114, 228, 
248 

Alcohol, 54, 203, 212, 232 
Alcoholism, 137 
Alkalies, 51-53, 259, 281 
Alkapton, 217, 239 
Altitude, 20 
Amaurosis, 123 
Amblyopia, 95, 123 
Ammonia, 55, 61, 224, 227 
Amyl nitrite, 51, 55 
Analgesia, 91 
Anatomy of blood, 101 

of brain, 95, 96 
of gastro-intestinal tube, 
108 

of heart, 100 
of kidneys, 116 
of liver, 110 
of lungs, 103 
of muscles, 128 
of nerves, 97, 98 
of ovaries, 118 
of pancreas, 108 
of skin, 126 

of spinal marrow, 96, 97 
of spleen, 113 
of testicles, 118 
of uterus, 118 
of vessels, 101 
Anesthesia, 91 
Aneurysms, 35 
Angina pectoris, 99 
Anhidrosis, 79, 91, 126 
Annulus Vieusseni, 34 
Anorexia, 80, 107 
Anthrax, 63 

Aromatic substances, 172 
Arsenic, 53, 203, 280 
Arterial blood, sugar of, 182, 188 
Arteriosclerosis, 99 
Artery, ligation of femoral, 38 

of gastroepiploic, 49 
of splenic, 49 
Asphyxia, 38, 55, 158 
Assimilation, 200, 203, 241 
Asteatosis, 79, 126 

307 







3°8 


INDEX. 


Asthenopia, 124 

Atrophy, acute yellow, of the liver, 49 
Autophagia, 81, 168 
Azoturia, 228 

B. 

Balanitis, 118 
Balanoposthitis, 118, 160 
Basophilia, perinuclear, 102 
Bile, 49 

Blood, acids in, 133, 224 
corpuscles, 101 
glycogen in, -177 
hemoglobin of, 138 
specific gravity of, 101 
sugar of, 187 
tests of, 244 
Bones, 128 

Brain, 32, 35, 36, 86, 95 
Bread, 274 
Breath, 84 
Bulimia, 79 
Butter, 271 

Butyric acid. See Acid, Butyric. 

C. 

Cachexia, 68 

Calculi in gall-ducts, 37, 49, 79 

in kidneys and urinary ducts, 

ri 5 

in pancreas, 109 
Calories, 232 

Cane-sugar. See Saccharose. 
Carbohydrate, 24, 57, 105, 170, 184, 
232 

Carbon dioxid. See Acid, Carbonic. 

monoxid, 56 
Carbuncle, 83 
Casts, renal, 248 
Cataract, 119-121, 160 
Chalazion, 124 
Chloral, 51, 55 
Chloralamid, 51, 55 
Chloroform, 55 
Cholera, 63, 64 
Chorea, 35 
Circulation, 98 
Cirrhosis of kidneys, 115 
of liver, 50, 137 
of pancreas, 109, 137 
Classes, social, 22 
Climate, 20 
Cold, 20, 68 

Coma, 85, 131—133, 161, 258 
Constipation, 106, 258 
Cramp, 89 

Crises gastriques, 106 
Croup, 63, 158 


Crura cerebelli, 31, 32 
cerebri, 32 
Crystallose, 279 
Curare, 57 

Cysticercus racemosus, 35 
Cystitis, 115 

D. 

Decubitus, 83 

Deiter’s nucleus, 31 

Delphinin (^methyl delphinin), 57 

Dextrin, 170, 219 

Diabetes alternans, 44, 216 

bronze-colored, 137, 138 
constitutional, 136 
decipiens, 78 
fat, 136 

gastro-intestinal, 137 
gouty, 136 
hepatogenic, 137 
herpetic, 136 
in animals, 15 
infantilis, 157-164 
insipidus, 28, 39, 67 
mild, 10, 129, 202, 220 
muscular, 137 
neurogenic/ 134 
pancreatic, 134, 164-169 
periodic, 44 
renal, 137 

severe, 10, 130, 202, 220 
Diacetic acid. See Acid, Diacetic. 
Diamins, 220 
Diet, 203, 227, 261 
Digestion, 104, 170 
Digestive organs, 104-114 
Dilatation of stomach, 104 
Diphtheria, 62, 158 
Diplopia, 95 
Disaccharids, 170 
Distribution of diabetes, 16-18 
Diuretin, 58 
Dysentery, 62 

E. 

Ears, 124 

Eczema, 41, 91, 124, 127 
Electrotherapy, 292 
Emotions, 22, 37, 38, 159, 203 
Encephalomalacia, 36 
Endarteritis, 97, 101, 138 
Energy. See Vital Force. 
Enuresis, 158 
Epilepsy, 36, 86 
Episcleritis, 124 
Erysipelas, 63, 84 
Erythema, 127 

nodosum, 63 




INDEX. 


309 


Ether, 55 

Etiology of diabetes mellitus, 16-25. 
(Race—mode of life—sex—age— 
climate—heredity—profession —ex¬ 
cesses—emotions—sedentary life— 
diet—exposure—trauma—sunstroke 
—adiposity—gout.) 

Excesses, 22, 23, 203 
Exophthalmic goiter, 36, 86 
Exposure, 24 
Exudates, 203 
Eyes, 118-124 

F. 

Fat, 60, 105, 170, 171, 184, 209, 212, 
232 

Fatigue, 68, 203 
Feces, 58, 105, 135 
Fermentation, 000 
Ferments in blood, 180, 191 
in liver, 179 
in urine, 220 

Fesselungsglycosurie, 38 
Fever, 166, 203 
Fibrin, 57 
Food, 170, 189 

Frequency of diabetes mellitus, 15-18 
Furunculosis, 41, 83 

G. 

Galactose, 207, 240 
Gall-stones, 37, 49, 79, 112 
Ganglion, celiac, 34, 35 

inferior cervical, 34 
superior cervical, 34 
thoracic, 34 

Gangrene, 81, 91, 103, 293 
Gastric juice, 108 
Gingivitis, 85 
Glands, gastric, 108 
peptic, 108 
salivary, 38 
thyroid, 38 

Glucose, 167, 170, 184, 206, 232, 239 
Glycemia, 29, 188 

Glycogen, 52, 97,^168, 170, 172, 173- 
180 

Glycolysin, 191 

Glycolysis, 191—193 

Glycosuria, alimentary, 29, 48, 173, 

199 • 

cachectic, 68 
cardiac, 28, 58 
concomitant, 28 
experimental, 31 
fatigue, 68 
fetal, 66 
from cold, 68 


Glycosuria, gouty, 67 

hepatogenous, 48 
in animals, 37 
marasmic, 68 
nervous, functional, 37- 
48 

organic, 30-37 
pancreatic, 165, 166 
puerperal, 65 
renal, 69 
senile, 68 

simple, 9, 42-48, 242 
starvation, 67 
toxic, 50-62. (From acids 
—metals and salts of 
alkalies, phosphorus, 
arsenic, mercury, lead, 
uranium — alcohol, 
ether, chloroform, 
chloral, chloralamid, 
amyl nitrite, ammonia 
—carbonic acid, car¬ 
bon monoxid—curare, 
strychnin, delphinin, 
morphin, veratrin, er- 
gotin, caffein—diuretics 
thyroidin, tuberculin, 
pancreatin, fecal ex¬ 
tract—phloridzin and 
phloretin.) 

Glycosurias, 26, 204 
Glycosuric acid. See Acid, Glycosuric. 
Glycuronic acid. See Acid , Glycu- 
ronic. 

Gout, 25, 39, 67 

Graves’ disease. See Exophthalmic 
Goiter. 

Gum, animal, 219, 240 
Gummata, 63 
Gums, 85 

H. 

Hair, 127 
Heart, 98, 100 
Hemianopsia, 95 
Hemoglobin, 138 
Hemorrhage, 94, 100, 124 
Hemosiderosis, 101, 138 
Heredity, 21, 159 
Herpes, 91, 124, 127 
History, 10-15 

Homogentisinic acid. See Acid, Ho- 
mogentisinic . 

Hordeolum, 124 
Hunger, 79 
Hydrotherapy, 290 
Hygiene, 255 

Hyperesthesia, 90, 124, 125 





3io 


INDEX. 


Hyperglycemia, 29, 48, 49, 56, 57, 71, 
165, 190 

Hyperidrosis, 91 
Hypermetropia, 121 
Hypochondriasis, 87 
Hypoglycemia, 29, 33, 49, 56, 61 
Hysteria, 88 

I. 

Ichthyosis, 127 

Icterus, 53 

Impetigo, 127 

Impotence, 117 

Incontinence. See Enuresis. 

Infection, 25 

Infectious diseases, 62, 159 
Influenza, 62, 64 
Inosit, 207 
Insomnia, 41, 256 
Inulin, 207 
Invertin, 170 
Iridocyclitis, 123 
Iritis, 123 
Irritability, 41 
Isomaltose, 219 

K. 

Keratitis, 123 
Kidneys, 69, 114-117 
Knee-jerk. See Reflexes. 

Kreatin, 217 
Kreatinin, 217, 239 

L. 

Lactaciduria, 53, 57 
Lactose, 62, 66, 167, 171, 206, 208, 
232, 239 

Lactosuria, 65, 199 
Laios, 208 
Lassitude, 128 
Lead, 53 
Leucin, 219 
Leukemia, 68 
Leukocytes, 177, 178 
Leukocytosis, 101 

Levulose, 167, 171, 206, 208, 239, 279 

Levulosuria, 167, 199 

Lichen, 127 

Life-insurance, 243 

Lipaciduria, 218 

Lipemia, 102, 212 

Lipuria, 212, 218 

Liver, 48, 50, 57, 59, no, 137, 173, 
214 

Lobus diabeticus, 31, 32 
hydruricus, 31, 32 
opticus, 32 
Lungs, 103 


Luxuries, 23 
Lymphangitis, 84 
Lyssa, 63 

M. 

Malaria, 62, 64, 137 
Mai perforant, 83, 91 
Maltose, 167, 170, 209, 219, 239 
Maltosuria, 135, 199, 209 
Mannite, 207 

Marasmus, 68, 102, 161, 204 
Marriage, 254 
Massage, 203, 290 
Mastication, 104 
Masturbation, 158 
Measles, 62 
Mechanotherapy, 289 
Melancholia, 87 
Meningitis, 35 
Meningomyelitis, 36 
Mental treatment, 255 
Mercury, 53 
Metabolism, 168 
Metallic salts, 53 
Migraine, 89 
Milk, 276 

Milk-sugar. See Lactose. 
Monosaccharids, 170 
Morbus gravesi. See Exophthalmic 
Goiter. 

Morphin, 57, 61 
Mouth, 79, 84 
Mucin, 214, 215 
Muscles, 128, 203 
Mydriasis, 121 
Myelitis, 36 
Myocardium, 99 
Myopia, 121 

N. 

Nails, 91, 128 
Nephritis, 60 
Nephrolithiasis, 115 
Nerve, abducent, 95 
crural, 91 

depressor of the pneumogas- 
tric, 33 
dorsal, 34 
facial, 95 
oculomotor, 95 
optic, 122 

pneumogastric, 31, 33 
sciatic, 33 
splanchnic, 34 
supraorbital, 89 
sympathetic, 34,98, 183 
tibial, 97 

Nervous symptoms, 86-95 
Neuralgia, 37, 88, 158 



INDEX. 


31 I 


Neurasthenia, 39, 70, 88, 106 
Neuritis, 90, 97, 102 
Neuroses, 36, 37, 87, 106 
Neurotabes, 94 
Nitrobenzol, 51 
Nitrogen, 166, 170, 233 
Nitrotoluol, 51 
Nuclein, 214, 215 
Nutritive needs, 168, 232, 260 


O. 

Obesity, 25, 39, 66 
Oidium albicans, 160 
Operations, 292 
Ophthalmic goiter, 86 
Opium, 203, 280 
Orchitis, 118 
Organotherapy, 288 
Osteomalacia, 231 
Osteoporosis, 85, 129 
Otalgia, 125 
Otitis, 124, 125 
Ovaries, 118 

Oxalic acid. See Acid , Oxalic. 
Oxaluria, 41, 45, 218 
/?-Oxybutyric acid. See Acid , fi-oxy- 
butyric. 

Oxygen, 234 

P. 

Pancreas, 108, 164-169 
Pancreatic juice, 105, 168 
Pancreatin, 58 
Paralysis, 91 

agitans, 35 

general, progressive, 35 
Paraplasma, 57, 172 
Paraplegia, 91 
Paresthesia, 88 
Paronychia, 128 
Pedunculi cerebelli, 32 
cerebri, 32 
Pemphigus, 127 
Pentoses, 175, 215, 219, 240 
Peptonuria, 53 
Pericementitis, 85 
Periostitis, 85 
Perspiration, 231 
Pertussis, 63, 158 
Petechiae, 127 
Phenacetin, 203 
Phimosis, 118, 160 
Phlegmon, 84 
Phloretin, 59 
Phloridzin, 59, 166 
Phloroglucin, 59 


Phlorose, 59 
Phosphaturia, 230 
Phosphorus, 49 

Phthisis (pulmonary tuberculosis), 102 

Pigment, 138 

Piqure, Bernard’s, 31 

Pityriasis, 127 

Pneumaturia, 115 

Pneumonia, 63, 103, 161 

Pollakiuria, 41, 78 

Polydipsia, 76 

Polyneuritis, 90 

Polyuria, 31, 58, 76, 207 

Potatoes, 276 

Potency, sexual, 89 

Pregnancy, 66, 118, 254 

Presbyopia, 121 

Professions, 21 

Prognosis, 63, 138-141, 160 

Prophylaxis, 253 

Propionic acid. See Acid , Propionic. 
Proteids, 57, 105, 170, 171, 184, 201, 
212, 232 
Pruritus, 126 

Pseudo angina pectoris, 99 
Pseudotabes, 93 
Psoriasis, 127 
Psychoneuroses, 21, 87 
Ptomains, 220 
Ptosis, 95 
Pulse, 77, 98, 131 
Pupil, Argyll Robertson, 92 
Purpura, 127 
Pylethrombosis, 49 
Pyorrhea, alveolar, 85 
Pyrocatechin, 5, 217 


Q- 

Quotient of respiration, 185, 235 


R. 

Race, 17 

Raynaud’s disease, 83, 91 
Recovery, 65, 160 
Reflexes, 92 
Remedies, 280 
Respiration, 131,234 
Respiratory organs, 102 
Retinitis, 122 
Rupia, 127 

S. 

Saccharids, 170, 174 
Saccharin, 279 

Saccharomyces apiculatus, 239 



312 


INDEX. 


Saccharose, 167, 170, 206, 232 

Saccharosuria, 46, 47, 199, 201 

Salicylic acid. See Acid, Salicylic. 

Saliva, 104, 202 

Sanatoriums, 256 

Scarlet fever, 62, 158 

Sciatica, 36, 88 

Scleritis, 124 

Sclerosis, multiple, 35 

Secretions, 79, 104 

Sedentariness, 23 

Senility, 68 

Sensibility, 91 

Sex, 19, 159 

Simulation, 252 

Sleep, 32, 256 

Spinal cord, 32, 36, 57, 91, 96, 97 
Spleen, 113 
Spondylitis, 37 
Sputa, 203' 

Stages of diabetic dystrophy, 9, 10, 
42-47, 129 

Starch, 52, 170, 206, 232 
Starvation, 24, 67, 159, 167, 183, 203 
Sterility, 118 
Stools, 105, 134 

Strains, emotional and intellectual, 22 
Strychnin, 51, 57 
Sugar in blood, 10, 187 
in liver, 11, 180 
in urine, 9, 11, 73. See Galac¬ 
tose, Glucose, Lactose , Levu- 
lose, Maltose, Saccharose. 
Sulphates, 172 
Sulphonal, 56 

Sulphuric acid. See Acid, Sulphuric. 
Sunstroke, 25 
Sweat, 202 
Sweets, 24, 158 

Symptoms of diabetes, 70-138 

Syphilis, 35, 63, 287 

Syzygium jambulanum, 62, 168, 284 


T. 

Tabes dorsalis, 35 
Tears, 202 
Teeth, 42, 85 
Temperature, 85, 160 
Test, Barfoed’s (glucose), 239 

Bernard-Seegen’s (glucose), 238 
Biebrich’s (blood, color), 245 
Bremer’s (blood, color), 244 
Ehrlich-Biondi’s (blood, color), 
245 

Esbach’s (albumin), 248 
Fischer’s (glucose), 237 


Test, Gerhardt’s (diacetic acid), 11,71, 
240, 247 

Heller’s (albumin), 248 
Kjeldahl’s (nitrogen), 248 
Nylander’s (glucose), 237, 239 
Robert’s (glucose), 247 
Troemmer’s (glucose), 237 
Williamson’s (blood, color), 245 
Worm-Mtiller’s (glucose), 237 
Testicles, 118 

Theories, 12-14, 179, 194-198 
Thirst, 42, 76 
Thyroidin, 58 
Tongue, 84 
Toxins, 71, 220, 221 
Transmutation, 86 
Trauma, 32, 140, 159 
Tuberculin, 58 

Tuberculosis, 68, 102, 137, 161 
Tumors (new growths), 35 
Typhoid, 62, 64 
Tyrosin, 219 


U. 

Urea, 216 
Uric acid, 216, 239 
Urinary organs, 114-117 
Urine, 73-76, 160 
color, 75 
density, 75 
quantity, 77, 246 
specific gravity, 75, 246 
substances in. See under the 
different headings: Acetone, 
Albumin, Alkapton, Ammo¬ 
nia, Butyric Acid, Casts 
(renal), Dextrin, Diacetic 
Acid, Diamins, Fatty 
Acids, Ferment, Glycogen, 
Glucose, Glycosuric Acid, 
Glycuronic Acid, Gum, Hip- 
puric Acid, Homogentisinic 
Acid, Indoxyl, Inosite, Iso¬ 
maltose, Lactic Acid, Lactose, 
Laios, Levulose, Leucin, 
Maltose, Oxalic Acid, ( 3 - Oxy- 
butyric Acid, Pentoses, Pto- 
mains , Pyrocatechin, Reduc¬ 
ing Substances, Saccharose, 
Skatoxyl, Sulphuric Acid (in 
sulphates and coupled ), Tox¬ 
ins, Urea, Uric Acid, Uro¬ 
bilin, Urochloralic Acid, Uro- 
leucin. 
toxicity, 220 
Urobilin, 219 
Urochloralic acid, 239 










INDEX. 


313 


Uroleucin, 219 
Urticaria, 91 
Uterus, 118 

V. 

Vaccinia, 63 
Variola, 63 
Vein, portal, 181, 189 
Veins, hepatic, 181, 182, 188 
in general, 181, 188 
Ventricle, fourth, of the brain, 31, 95 
(stomach), 104 
Veratrin, 51, 58 
Vermis, 32 

Vessels, arterial, 181, 188 


Virility, 41 
Vital force, 184-187 
Vulnerability, 81 
Vulvitis, 118, 160 


W. 

Water, 231, 278 
Weighing, 249 
Weight of body, 80 


X. 

Xanthoma tuberosum diabeticum, 127 


21 




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MEDICAL AND SCIENTIFIC PUBLICATIONS. 


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PHYSICIAN S VISITING LIST. Published Annually. Forty-eighth Year (1800) 
of its Publication. v ** 

^ erea fter all styles will contain the interleaf or special memoranda page, except 
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rr\ *< << a a a T 

5 ° • • • • I • 

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SANSOM. Diseases of The Heart. The Diagnosis and Pathology of Diseases of 
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SMITH. Electro-Chemical Analysis. By Edgar F. Smith, Professor of Chem¬ 
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*** See also Oettel and Richter. 

SMITH and KELLER. Experiments. Arranged for Students in General Chem¬ 
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SMITH. Dental Metallurgy. A Manual. By Ernest A. Smith, f.c.s., Asst. 
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University, Manchester. Examiner in Physiology, Universities of Edinburgh 
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STIRLING. Outlines of Practical Histology. 368 Illustrations. Second Edi¬ 
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STOHR. Text-Book of Histology, Including the Microscopical Technic. 

By Dr. Philipp Stohr, .Professor of Anatomy at University of Wurzburg. 
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and Embryology, Woman’s Medical College of Pennsylvania. Edited, with 
Additions, by Dr. Alfred Schaper, Demonstrator of Histology and Embry¬ 
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German Edition, Enlarged and Revised. 292 Illustrations. Octavo. Cloth, $3.00 

STRAHAN. Extra-Uterine Pregnancy. The Diagnosis and Treatment of Extra- 
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SUTTON’S Volumetric Analysis. A Systematic Handbook for the Quantitative 
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Cloth, $4.50 

SWAIN. Surgical Emergencies, together with the Emergencies Attendant on 
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149 Illustrations. Cloth, $ 1-75 

SWANZY. Diseases of the Eye and their Treatment. A Handbook for Physi¬ 
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the National Eye and Ear Infirmary ; Ophthalmic Surgeon to the Adelaide Hos¬ 
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“ Is without doubt the most satisfactory manual we have upon diseases of the eye. It occu¬ 
pies the middle ground between the students’ manuals, which are too brief and concise, and the 

encyclopedic treatises, which are too extended and detailed to be of special use to the general 

practitioner .”—Chicago Medical Recorder. 

SYMONDS. Manual of Chemistry, for Medical Students. By Brandreth 
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T „ mo b ' Cloth, $2.00 


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TALBOT. Irregularities of the Teeth, and Their Treatment, by Eugene S. 
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TANNER’S Memoranda of Poisons and their Antidotes and Tests. By Thos. 
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TAYLOR Practice of Medicine. A Manual. By Frederick Taylor, m.d., 
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Evelina Hospital for Sick Children, and Examiner in Materia Medica and Phar¬ 
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P. BLAKISTON'S SON &- CO.'S 


TAYLOR AND WELLS. Diseases of Children. A Manual for Students and 
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Cloth, $4.00 

TEMPERATURE Charts for Recording Temperature, Respiration, Pulse, Day of 
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THOMPSON. Urinary Organs. Diseases of the Urinary Organs. Containing 32 
Lectures. By Sir Henry Thompson, f.r.c.s., Emeritus Professor of Clinical Sur¬ 
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470 pages. Cloth, $3.00 

THORINGTON. Retinoscopy (The Shadow Test) in the Determination of 
Refraction at One Metre Distance with the Plane Mirror. By James Thoring- 
ton, a.m., m.d., Adjunct Professor of Diseases of the Eye in the Philadelphia Poly¬ 
clinic ; Assistant Surgeon Wills Eye Hospital; Associate Member American 
Ophthalmological Society; Ophthalmologist to the Elwyn and Vineland Train¬ 
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the Philadelphia Manual Training Schools, etc. With 38 Illustrations, several 
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Refraction and How to Refract. With 200 Illustrations, most of which 
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Synopsis of Contents. —I. Optics. II. The Eye; The Standard Eye; 
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Far and Near Point; Determination of Distant Vision and Near Point; Ampli¬ 
tude of Accommodation; Convergence; Angle Gamma; Angle Alpha. III. 
Ophthalmoscope; Direct and Indirect Method. IV. Emmetropia ; Hyperopia; 
Myopia. V. Astigmatism or Curvature Ametropia ; Tests for Astigmatism. VI. 
Retinoscopy. VII. Muscles. VIII. Cycloplegics; Cycloplegia; Asthenopia; 
Examination of the Eyes. IX. How to Refract. X. Applied Refraction. XL 
Presbyopia; Aphakia; Anisometropia; Spectacles. XII. Lenses; Spectacle 
and Eye Glass Frames; How to Take Measurements for Them and How They 
Should be Fitted. 

THORNE. The Schott Methods of the Treatment of Chronic Diseases of the 
Heart. With an Account of the Nauheim Baths and of the Therapeutic Exer¬ 
cises. By W. Bezly Thorne, m.d., m.r.c.p. With Plates and Numerous 
Other Illustrations. Third Edition, Revised and Enlarged. Octavo. Cloth, $1.75 

TOMES’ Dental Anatomy. A Manual of Dental Anatomy, Human and Compara¬ 
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Dental Surgery. A System of Dental Surgery. By John Tomes, f.r.s. 
Fourth Edition, Thoroughly Revised. By C. S. Tomes, d.d.s. With 289 
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TREVES. German-English Medical Dictionary. By Frederick Treves, f.r.c.s., 
assisted by Dr. Hugo Lang, b.a. (Munich). i2mo. ]/ 2 Russia, $3.25 

Physical Education, Its Effects, Value, Methods, etc. Cloth, .75 

TUKE. Dictionary of Psychological Medicine. Giving the Definition, Ety¬ 
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Symptoms, Pathology, and Treatment of the recognized forms of Mental Dis¬ 
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27 


MEDICAL AND SCIENTIFIC PUBLICATIONS. 


TRAUBE. Physico-Chemical Methods. By Dr. J. Traube, Privatdocent in 
tlie lech meal High School of Berlin. Authorized Translation by W. D. Har- 

amson Senior Fellow in Chemistry, University of Pennsylvania. With 
97 Illustrations. 8vo. Cloth, $1.50 

THRESH. Water and Water Supplies. By John C. Thresh, d.s.c. (London), 
m.d., d p.h. (Cambridge), Medical Officer of Health to the Essex County 

ouncil; Lecturer on Public Health, King’s College, London; Fellow of the 
Institute of Chemistry ; Member Society Public Analysts, etc. Second Edition. 
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^^^'^I^UI'I' S Artificial Anaesthesia. A Manual of Anesthetic Agents in the 
Treatment of Diseases also their Employment in Dental Surgery ; Modes of Ad¬ 
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ph.g., Aural Surgeon to Jefferson College Hospital, etc. Fourth Edition, Re¬ 
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TUSON. Veterinary Pharmacopoeia, including the outlines of Materia Medica 
and Therapeutics. By Richard V. Tuson, late Professor at the Royal Veter¬ 
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Cloth, $2.25 

TUSSEY. High Altitude Treatment for Consumption. The Principles or 
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Successfully Treated in the Environment to which They were Accustomed 
Previous to Their Illness. By A. Edgar Tussey, m.d., Adjunct Professor of 
Diseases of the Chest in the Philadelphia Polyclinic and School for Graduates 
in Medicine, etc. i2mo. Cloth, $1.50 

TYSON. The Practice of Medicine. A Text-Book for Physicians and Students, 
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the University and to the Philadelphia Hospitals, etc. With Colored Plates and 
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“ Pew teachers in the country can claim a longer apprenticeship in the laboratory and at 
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nearly thirty years. Moreover, he entered medicine through the portal of pathology, a decided 
advantage in the writer of a text-book. . . . The typography is decidedly above works of 

this class issued from our publishing houses. There is no American Practice of the same attrac¬ 
tive appearance. The print is unusually sharp and clear, and the quality of the paper particu¬ 
larly good. . . . It is a piece of good, honest work, carefully conceived and conscientiously 

carried out.”— University Medical Magazine. 

*** Sample Pages and Illustrations Sent Free upon Application. 

Guide to the Examination of Urine. Ninth Edition. For the Use of 

Physicians and Students. With Colored Plate and Numerous Illustrations 
Engraved on Wood. Ninth Edition. Revised. i2mo. 276pages. Cloth, $1.25 
*** A French translatio?i of this book has recently appeared in Paris. 

Handbook of Physical Diagnosis. 3d Edition. Revised and Enlarged. 
With Colored and other Illustrations. i2mo. 278 pages. Cloth, $1.50 

Cell Doctrine. Its History and Present State. Second Edition. Cloth, $1 .50 

UNITED STATES PHARMACOPOEIA. 1890. Seventh Decennial Revision. 
Cloth, $2.50 (Postpaid, $2 .77); Sheep, $ 3.00 (Postpaid, $3.27); Interleaved, 
I4.00 (Postpaid, $4.50); printed on one side of page only. Unbound, #3.50 (Post¬ 
paid, $3.90). 

Select Tables from the U. S. P. (1890). Being Nine of the Most Important 
and Useful Tables, printed on Separate Sheets. Carefully put up in Patent 
Envelope. * 2 5 





From the Southern Clinic. 

“ We know of no series of books issued by any house that so fully meets our approval as these 
? Quiz-Compends ?. They are well arranged, full, and concise, and are really the best line of text¬ 
books that could be found for either student or practitioner.” 


BLAKISTON’S ?QUIZ=COMPENDS? 

The Best Series of Manuals for the Use of Students. 

Price of each, Cloth, . 80 . Interleaved for taking Notes, $ 1 . 25 . 

These Compends are based on the most popular text-books and the lectures of promi¬ 
nent professors, and are kept constantly revised, so that they may thoroughly represent the 
present state of the subjects upon which they treat. The authors have had large experience as 
Quiz-Masters and attaches of colleges, and are well acquainted with the wants of students. They 
are arranged in the most approved form, thorough and concise, containing over 600 fine illustra¬ 
tions, inserted wherever they could be used to advantage. Can be used by students of any 
college, and contain information nowhere else collected in such a condensed, practical shape. 

ILLUSTRATED CIRCULAR FREE. 

No. I. HUMAN ANATOMY. Sixth Revised and Enlarged Edition. Including Vis¬ 
ceral Anatomy. Can be used with either Morris’s or Gray’s Anatomy. 117 Illustrations 
and 16 Lithographic Plates of Nerves and Arteries, with Explanatory Tables, etc. By 
Samuel O. L. Potter, m.d., Professor of the Practice of Medicine, College of Physicians 
and Surgeons, San Francisco; late A. A. Surgeon, U. S. Army. 

No. 2. PRACTICE OF MEDICINE. Parti. Sixth Edition, Revised, Enlarged, and 
Improved. By Dan’l E. Hughes, m.d., Physician-in Chief, Philadelphia Hospital, late 
Demonstrator of Clinical Medicine, Jefferson Medical College, Philadelphia. 

No. 3. PRACTICE OF MEDICINE. Part II. Sixth Edition, Revised, Enlarged, and 
Improved. Same author as No. 2. 

No. 4. PHYSIOLOGY. Ninth Edition, with new Illustrations and a table of Physio¬ 
logical Constants. Enlarged and Revised. By A. P. Brubaker, m.d., Professor of 
Physiology and General Pathology in the Pennsylvania College of Dental Surgery; Demon¬ 
strator of Physiology, Jefferson Medical College, Philadelphia. 

No. 5. OBSTETRICS. Sixth Edition. By Henry G. Landis, m.d. Revised and Edited 
by Wm. H. Wells, m.d., Instructor of Obstetrics, Jefferson Medical College, Philadelphia. 
Enlarged. 3 Plates and 47 other Illustrations. 

No. 6. MATERIA MEDICA, THERAPEUTICS, AND PRESCRIPTION 
WRITING. Sixth Revised Edition (U. S. P. 1890). By Samuel O. L. Potter, m.d., 
Professor of the Practice of Medicine, College of Physicians and Surgeons, San Francisco. 

No. 7. GYNECOLOGY. Second Edition. By Wm. H. Wells, m.d., Instructor of Ob¬ 
stetrics, Jefferson Medical College, Philadelphia. 140 Illustrations. 

No. 8. DISEASES OF THE EYE AND REFRACTION. Second Edition. Includ¬ 
ing Treatment and Surgery and a Section on Local Therapeutics. By George M. Gould, 
m.d., and W. L. Pyle, m.d. With Formulae, Glossary, several useful Tables, and 109 
Illustrations, several of which are colored. 

No. 9. SURGERY, Minor Surgery, and Bandaging. Fifth Edition, Enlarged and Im¬ 
proved. By Orville Horwitz, b.s., m.d., Clinical Professor of Genito-Urinary Surgery 
and Venereal Diseases in Jefferson Medical College; Surgeon to Philadelphia Hospital, etc. 
With 98 Formulae and 167 Illustrations. 

No. 10. MEDICAL CHEMISTRY. Fourth Edition. Including Urinalysis, Animal 
Chemistry, Chemistry of Milk, Blood, Tissues, the Secretions, etc. By Henry Leffmann, 
m.d., Professor of Chemistry in Pennsylvania College of Dental Surgery and in the 
Woman’s Medical College, Philadelphia. 

No. 11. PHARMACY. Fifth Edition. Based upon Prof. Remington’s Text-Book of Phar¬ 
macy. By F. E. Stewart, m.d., ph.g., late Quiz-Master in Pharmacy and Chemistry, 
Philadelphia College of Pharmacy; Lecturer at Jefferson Medical College. 

No. 12. VETERINARY ANATOMY AND PHYSIOLOGY. Illustrated. By 

Wm. R. Ballou, m.d., Professor of Equine Anatomy at New York College of Veterinary 
Surgeons; Physician to Bellevue Dispensary, etc. With 29 graphic Illustrations. 

No. 13. DENTAL PATHOLOGY AND DENTAL MEDICINE. Third Edition, 

Illustrated. Containing all the most noteworthy points of interest to the Dental Student and 
a Section on Emergencies. By Geo. W. Warren, d.d.s., Chief of Clinical Staff, Pennsyl¬ 
vania College of Dental Surgery, Philadelphia. 

No. 14. DISEASES OF CHILDREN. Colored Plate. By Marcus P. Hatfield, 
Professor of Diseases of Children, Chicago Medical College. Second Edition, Enlarged. 

No. 15. GENERAL PATHOLOGY AND MORBID ANATOMY. 91 Illustra¬ 
tions. By H. Newberry Hall, ph.g., m.d., Professor of Pathology and Medical Chem¬ 
istry, Chicago Post-Graduate Medical School. Second Edition. 

No. 16. DISEASES OF THE SKIN. By Jay F. Schamberg, m.d., Instructor at 
Philadelphia Polyclinic. 99 Illustrations. 

Price, each, strongly bound in cloth, . 80 . Interleaved for taking Notes, $ 1 . 25 . 



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The changes and improvements made in 1896 met with such general 
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CONTENTS. 

PRELIMINARY MATTER. —Calendar, 1900-1901—Table of Signs, to be used in keeping records— 
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All these prices are net. No discount can be allowed retail purchasers. 

Circular and sa7nple pages upon application. 


5 ° 

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Morris’ 

Text-Book of Anatomy 

SECOND EDITION 

Thoroughly Revised and Greatly Improved 
790 Illustrations, of which many are in Colors 

Royal Octavo. Cloth, $6.00; Sheep, $?.00; Half Russia, $8.00 


Two Reviews Recently Published 
by Two Leading Medical Journals 


From 

The Medical Record, New York. 

“ The reproach that the English lan¬ 
guage can boast of no treatise on anatomy 
deserving to be ranked with the masterly 
works of Henle, Luschka, Hyrtl, and 
others, is fast losing its force. During 
the past few years several works of great 
merit have appeared, and among these 
Morris’s “ Anatomy ” seems destined to 
take the first place in disputing the palm 
in anatomical fields with the German 
classics. The nomenclature, arrange¬ 
ment, and entire general character re¬ 
semble strongly those of the above-men¬ 
tioned handbooks, while in the beauty 
and profuseness of its illustrations it sur¬ 
passes them. This edition offers but few 
changes ; a chapter on the skin has been 
added, and a useful list of vestigial and 
abnormal structures has been compiled. 
Sections especially worthy of praise are 
those on surgical and topographical anat¬ 
omy, and the chapter on the nervous 
system is presented with great clearness 
and fullness. The ever-growing popu¬ 
larity of the book with teachers and 
students is an index of its value, and it 
may safely be recommended to all inter¬ 
ested.” 


From 

The Philadelphia Medical Journal. 

“ Of all the text-books of moderate size 
on human anatomy in the English lan¬ 
guage, Morris is undoubtedly the most 
up-to-date and accurate. The changes 
from the first edition are not marked; 
perhaps the most noticeable feature is 
that there are twenty less cuts than in the 
first edition. Those which have been 
omitted, however, will not be greatly 
missed. The saving of space by the 
omission of a discussion of histology is a 
decided advantage, giving room for much 
matter of importance in these days when 
every student is obliged to own a special 
treatise on histology. To enumerate the 
numerous differences which are notice¬ 
able in the descriptions given by this book 
from those in many of the olderanatomies 
would require too much space. The 
changes, however, almost without excep¬ 
tion, tend toward an improved nomen¬ 
clature and greater accuracy. This is 
particularly noticeable in the parts de¬ 
voted to descriptions of the abdominal 
viscera and the joints. . . . For the stu¬ 
dent, the surgeon, or for the general prac¬ 
titioner who desires to review his anatomy, 
Morris is decidedly the book to buy.” 


***The illustrations in number, correctness, and excellence of execution 
are equaled by no similar treatise, about $1000 having been expended on 
new and improved blocks for this edition alone. Handsome circular free. 













































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